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MedMentor EDU
HIV INFECTION AND AIDS
Complete Exam-Oriented Medicine Notes
MedMentor EDU | Medicine Study Notes | Part II
MBBS · NEET-PG · INI-CET · DNB · FMGE
Compiled from Harrison's Principles of Internal Medicine · Davidson's Principles and Practice of Medicine · Kumar & Clark's Clinical Medicine · API Textbook of Medicine
Aligned with NACO / NTEP national guidelines and WHO recommendations
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CONTENTS AT A GLANCE 01. Introduction and Definitions 02. Classification of HIV 03. Epidemiology of HIV 04. Virology of HIV 05. Transmission of HIV 06. Pathogenesis of HIV Infection 07. Natural History of HIV Infection 08. Acute HIV Infection 09. Clinical Examination in HIV 10. HIV Testing and Diagnosis 11. Baseline Evaluation After Diagnosis 12. Monitoring of HIV 13. Clinical Staging and Classification 14. Presenting Problems in HIV 15. Organ-System Manifestations 16. Opportunistic Infections in HIV 17. Antiretroviral Therapy 18. Immune Reconstitution Inflammatory Syndrome 19. HIV-Associated Malignancies 20. Non-AIDS Comorbidities and Long-Term HIV Care 21. HIV in Special Populations 22. Prevention of Opportunistic Infections 23. Prevention of HIV 24. Diagrams, Clinical Photographs, Radiology & Slides 25. Important Viva Questions 26. High-Yield Exam Pearls |
HIV infection is a chronic, progressive infection caused by the Human Immunodeficiency Virus, a lentivirus of the family Retroviridae, characterised by infection and progressive depletion of CD4+ T lymphocytes, persistent immune activation and, in the absence of treatment, evolution to profound cellular immunodeficiency.
▪ Confirmed by demonstration of HIV antibodies, p24 antigen, HIV RNA or proviral DNA.
▪ Infection is lifelong — the virus integrates as provirus into the host genome and cannot presently be eradicated.
▪ With antiretroviral therapy (ART) the infection becomes a chronic manageable disease with near-normal life expectancy.
AIDS is the most advanced clinical stage of HIV infection, defined by the occurrence of any AIDS-defining opportunistic infection or malignancy, and/or a CD4 count < 200 cells/µL (or CD4 percentage < 14%) in a person with confirmed HIV infection.
▪ AIDS is a clinical–immunological syndrome, not a separate infection. [IMPORTANT]
▪ Corresponds to WHO Clinical Stage 4 and CDC Stage 3.
▪ Once a patient meets AIDS criteria the classification is permanent in CDC surveillance terms, even if CD4 recovers on ART. [COMMON MCQ]
▪ Preferred, non-stigmatising term for all persons with confirmed HIV infection, irrespective of clinical stage or treatment status.
▪ Terms such as "AIDS patient", "HIV victim" or "AIDS sufferer" are discouraged.
▪ Adults, adolescents and children ≥ 5 years: CD4 count < 200 cells/µL or WHO clinical stage 3 or 4.
▪ Children < 5 years: ALL children below 5 years presenting with HIV are considered to have advanced disease, except those who are already established and stable on ART.
▪ Triggers an accelerated "package of care" — TB screening, cryptococcal antigen (CrAg) screening, cotrimoxazole prophylaxis and rapid ART. [VERY HIGH-YIELD]
▪ Late presentation: first presentation with CD4 < 350 cells/µL or an AIDS-defining event, regardless of CD4.
▪ Presentation with advanced HIV disease: CD4 < 200 cells/µL or an AIDS-defining event.
▪ Late presentation is the single most important determinant of early mortality in Indian ART programmes.
▪ Virological suppression: plasma HIV RNA below the lower limit of detection of the assay used (commonly < 50 copies/mL; programme definition of success often < 1000 copies/mL).
▪ Undetectable viral load: HIV RNA not detected by a validated assay — the operational basis of U = U (Undetectable equals Untransmittable).
▪ Viral blip: isolated detectable HIV RNA (usually 50–200 copies/mL) with return to undetectable on repeat — not treatment failure.
▪ Low-level viraemia: persistent HIV RNA 50–1000 copies/mL.
▪ Virological failure: HIV RNA > 1000 copies/mL on two consecutive measurements ≥ 3 months apart, with adherence support, after ≥ 6 months on ART. [VERY HIGH-YIELD]
▪ Immunological failure: persistent CD4 < 250 cells/µL after clinical failure, or CD4 fall to or below baseline.
▪ Clinical failure: new or recurrent WHO stage 4 (or certain stage 3) conditions after ≥ 6 months of effective ART.
▪ Acute (primary) HIV infection: the period from acquisition until complete seroconversion — high viraemia, p24 antigenaemia, often symptomatic ("acute retroviral syndrome").
▪ Chronic HIV infection: established infection after seroconversion, encompassing clinical latency and symptomatic disease.
▪ Elite controllers: maintain HIV RNA < 50 copies/mL for > 12 months without ART; ≈ 0.5% of PLHIV. [FAVORITE EXAM QUESTION]
▪ Viraemic controllers: spontaneously maintain viral load 50–2000 copies/mL without ART.
▪ Long-term non-progressors (LTNP): ≥ 7–10 years of infection with stable CD4 > 500 cells/µL and no symptoms, without ART; ≈ 5%.
▪ Rapid progressors: progress to AIDS within 2–3 years of seroconversion; ≈ 10%.
▪ Serodiscordant (serodifferent) couple: one partner HIV-positive, the other HIV-negative — the key target for treatment-as-prevention and PrEP.
▪ HIV-exposed infant: infant born to, or breastfed by, a mother with HIV; requires early infant diagnosis (EID) and prophylaxis until infection is excluded.
▪ HIV-associated immunodeficiency: the acquired cellular immune defect resulting from CD4 depletion and immune dysregulation, graded by CD4 count/percentage.
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Difference Between HIV Infection and AIDS [COMMON MCQ] ▪ HIV infection = presence of the virus; may be entirely asymptomatic for a decade. ▪ AIDS = advanced stage of HIV infection defined by AIDS-defining illness and/or CD4 < 200 cells/µL. ▪ All persons with AIDS have HIV infection; most persons with HIV infection do not have AIDS. ▪ With early ART, the great majority of PLHIV never develop AIDS. |
▪ 1981 — First cluster of Pneumocystis pneumonia and Kaposi sarcoma reported among previously healthy young men in the USA.
▪ 1982 — The term Acquired Immune Deficiency Syndrome (AIDS) coined.
▪ 1983 — Virus isolated at the Institut Pasteur (LAV) by Barré-Sinoussi and Montagnier; independently as HTLV-III in the USA. [FAVORITE EXAM QUESTION]
▪ 1986 — Name HIV formally adopted; HIV-2 identified in West Africa.
▪ 1986 — First case of HIV in India detected in female sex workers in Chennai (Madras) by Dr Suniti Solomon and Dr Sellappan Nirmala. [VERY HIGH-YIELD]
▪ 1987 — Zidovudine (AZT) becomes the first licensed antiretroviral drug.
▪ 1992 — National AIDS Control Organisation (NACO) established in India.
▪ 1996 — Highly active antiretroviral therapy (HAART) transforms prognosis.
▪ 2004 — Free ART rollout begins in India through government ART centres.
▪ 2008 — Barré-Sinoussi and Montagnier awarded the Nobel Prize in Physiology or Medicine.
▪ 2015–2017 — "Treat All" policy adopted; HIV and AIDS (Prevention and Control) Act, 2017 enacted in India.
▪ 2017 onwards — Dolutegravir-based first-line ART scaled up globally and in the Indian national programme.
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Untreated Course of HIV Infection HIV acquisition ↓ Eclipse phase (7–14 days) — virus undetectable in blood ↓ Acute retroviral syndrome (2–4 weeks) — very high viraemia, transient CD4 fall ↓ Seroconversion and establishment of viral set point ↓ Clinical latency (median 8–10 years) — CD4 falls ≈ 50–80 cells/µL/year ↓ Symptomatic HIV (CD4 200–350) — TB, candidiasis, zoster, weight loss ↓ AIDS (CD4 < 200) — opportunistic infections and malignancies ↓ Death (median survival ≈ 1–2 years after AIDS onset without ART) |
▪ Effective ART produces durable viral suppression, immune reconstitution and near-normal life expectancy when started early.
▪ Mortality shifts from opportunistic infections towards non-AIDS comorbidities — cardiovascular disease, chronic liver and kidney disease, non-AIDS cancers.
▪ U = U: a person with sustained undetectable viral load does not transmit HIV sexually. [VERY HIGH-YIELD]
▪ Focus of care has moved to adherence, long-term toxicity, comorbidity screening, mental health and quality of life.
▪ HIV remains among the leading infectious causes of death worldwide despite dramatic declines since 2010.
▪ India has the third largest number of PLHIV in the world (after South Africa and Mozambique/Nigeria depending on the year of estimate). [COMMON MCQ]
▪ HIV–tuberculosis is the dominant clinical interaction in India; TB is the commonest opportunistic infection and commonest cause of death in Indian PLHIV. [VERY HIGH-YIELD]
▪ Targets: UNAIDS 95-95-95 by 2025 and elimination of AIDS as a public-health threat by 2030 (SDG 3.3).
▪ Cause of the global pandemic; responsible for > 95% of infections worldwide and almost all infections in India.
▪ Derived from SIVcpz of chimpanzees (Pan troglodytes troglodytes) and SIVgor of gorillas in West-Central Africa.
▪ More transmissible, higher viral loads, faster progression than HIV-2.
▪ Endemic to West Africa (Guinea-Bissau, Senegal, Gambia, Cape Verde, Côte d'Ivoire); sporadic in India, chiefly in Maharashtra and Gujarat.
▪ Derived from SIVsm of the sooty mangabey (Cercocebus atys). [COMMON MCQ]
▪ Characteristics: lower viral load, slower CD4 decline, longer latency, lower vertical and sexual transmission.
▪ Intrinsically resistant to all NNRTIs and to the fusion inhibitor enfuvirtide; reduced susceptibility to some protease inhibitors. [VERY HIGH-YIELD]
▪ Not detected by HIV-1 RNA assays — requires HIV-2 specific viral load or DNA PCR.
|
Feature |
HIV-1 |
HIV-2 |
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Distribution |
Worldwide (pandemic) |
West Africa; sporadic elsewhere |
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Simian ancestor |
SIVcpz / SIVgor |
SIVsm (sooty mangabey) |
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Transmissibility |
High |
Lower |
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Viral load |
High |
Low |
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Progression |
Faster |
Slower; many long-term non-progressors |
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Vertical transmission |
15–45% untreated |
1–4% |
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Unique gene |
vpu |
vpx |
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NNRTI activity |
Susceptible |
Intrinsically resistant |
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Enfuvirtide |
Active |
Not active |
▪ SIVs are lentiviruses naturally infecting > 40 African non-human primate species, usually non-pathogenic in their natural hosts.
▪ Cross-species transmission to humans occurred through hunting and butchering of bushmeat (cutaneous/mucous membrane exposure to infected blood).
▪ Molecular clock studies date the origin of HIV-1 group M to around 1920 in Kinshasa (Democratic Republic of Congo).
▪ At least 13 independent cross-species transmission events account for the recognised HIV-1 and HIV-2 groups.
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Group |
Origin |
Epidemiological significance |
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Group M (Major) |
SIVcpz — chimpanzee |
Cause of the global pandemic; > 90% of all HIV infections |
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Group N (Non-M, non-O) |
SIVcpz — chimpanzee |
Very rare; a handful of cases in Cameroon |
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Group O (Outlier) |
SIVgor — gorilla |
Cameroon, Gabon, Equatorial Guinea; ~1% of regional infections; may be missed by some assays |
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Group P |
SIVgor — gorilla |
Extremely rare; only a few cases from Cameroon |
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Mnemonic — HIV-1 Groups: "MNOP" M = Major (pandemic) · N = New/Non-M-non-O · O = Outlier · P = Pending/Putative Only Group M causes the pandemic. [FAVORITE EXAM QUESTION] |
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▪ Group M is divided into subtypes A, B, C, D, F, G, H, J, K (and L) — with sub-subtypes A1–A6, F1, F2.
▪ Subtype C — commonest worldwide (~50% of global infections); dominant in southern Africa, Ethiopia and India. [VERY HIGH-YIELD]
▪ Subtype B — Europe, Americas, Australia, Japan; the subtype on which most drug and vaccine research was based.
▪ Subtype A — East Africa, Eastern Europe and Russia.
▪ Subtypes D, F, G, H, J, K — mainly Central and West Africa.
▪ Arise when a single cell is infected by two different subtypes, allowing template switching by reverse transcriptase during replication.
▪ Designated by number and parent subtypes, e.g. CRF01_AE (Southeast Asia, north-east India), CRF02_AG (West Africa).
▪ Unique recombinant forms (URFs) are recombinants found in only a single individual.
▪ Recombination is a major driver of HIV diversity and complicates vaccine design and assay sensitivity.
▪ HIV-1 subtype C accounts for approximately 90–95% of infections in India. [VERY HIGH-YIELD]
▪ CRF01_AE predominates in the north-eastern states (Manipur, Nagaland), linked to injecting drug use and the Southeast Asian epidemic.
▪ Subtype A, subtype B and A/C and B/C recombinants occur sporadically.
▪ HIV-2 is uncommon (< 1%), reported mainly from Maharashtra, Gujarat and Goa.
▪ HIV-2 comprises groups A to I, each from an independent SIVsm transmission.
▪ Only groups A and B are epidemic; the rest are single or very few cases.
▪ Reported from West Africa and, rarely, from western India.
▪ Diagnosis requires discriminatory serology (HIV-1/HIV-2 differentiation assay) and type-specific nucleic acid tests.
▪ Therapeutic implication: the regimen must be active against both viruses — avoid NNRTIs; use 2 NRTIs + an INSTI or a boosted PI. [IMPORTANT]
▪ HIV-1 usually dominates virologically and drives disease progression.
▪ ~39–40 million people are living with HIV globally.
▪ New infections: ~1.3 million per year — a decline of nearly 60% from the 1995 peak.
▪ AIDS-related deaths: ~6.3–7 lakh (0.63–0.7 million) per year — a fall of about 70% from the 2004 peak.
▪ Global adult prevalence: ~0.7%.
▪ Approximately 86% of PLHIV know their status; 77% are on ART; 72% are virally suppressed (global cascade).
▪ Eastern and Southern Africa — the epicentre; > 50% of all PLHIV; generalised epidemic; female predominance.
▪ Western and Central Africa — second largest burden; lower ART coverage.
▪ Asia and the Pacific — third largest burden; concentrated epidemics in key populations.
▪ Eastern Europe and Central Asia, Middle East and North Africa, and Latin America — regions with rising new infections.
▪ Western Europe, North America, Australia — low prevalence, high ART coverage, epidemics concentrated in MSM and migrants.
▪ Adults (15+): ~37 million; children (< 15 years): ~1.4 million.
▪ Women and girls account for ~53% of all PLHIV globally; in sub-Saharan Africa adolescent girls and young women bear a strikingly disproportionate burden.
▪ Adolescents (10–19 years): ~1.7 million; the only age group in which AIDS deaths have not fallen commensurately.
▪ Young adults (15–24 years) account for approximately one-third of new infections.
▪ Pregnant women: ~1.3 million pregnancies per year in women with HIV; > 80% receive ART for prevention of vertical transmission.
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HIV Testing and Treatment Cascade (UNAIDS 95-95-95) All people living with HIV (denominator) ↓ 95% know their HIV status (testing cascade) ↓ 95% of those diagnosed are on antiretroviral therapy (treatment cascade) ↓ 95% of those on ART achieve viral suppression ↓ Net result: ~86% of all PLHIV virally suppressed → epidemic control |
▪ Trends in new infections: falling globally, but too slowly to meet 2025 targets; rising in Eastern Europe/Central Asia and MENA.
▪ Trends in AIDS deaths: steadily falling due to ART scale-up; TB remains the leading cause of HIV-related death worldwide.
▪ Viral suppression rates are lowest in children, adolescents and men in high-burden settings.
▪ Estimated ~25 lakh (2.5 million) people living with HIV in India — the third highest national burden globally. [COMMON MCQ]
▪ Adult (15–49 years) HIV prevalence ≈ 0.20–0.22% — a low-prevalence, concentrated epidemic. [VERY HIGH-YIELD]
▪ Annual new infections: ~60,000–70,000; annual AIDS-related deaths: ~35,000–42,000.
▪ India has achieved a >75% decline in new infections since 2010 — well above the global average.
▪ Highest adult prevalence: Mizoram (> 2%), Nagaland, Manipur, Meghalaya (north-east); Andhra Pradesh and Telangana in the south.
▪ Highest absolute numbers: Maharashtra, Andhra Pradesh, Telangana, Karnataka, Uttar Pradesh, Tamil Nadu.
▪ North-eastern epidemic — driven by injecting drug use and its sexual bridging.
▪ Southern/western epidemic — predominantly heterosexual transmission.
▪ Low-prevalence but rising states: Uttar Pradesh, Bihar, Gujarat, Rajasthan, Delhi and Punjab (the last also with an IDU component).
▪ Historically urban and peri-urban predominance, linked to migration, transport corridors and sex work.
▪ Progressive ruralisation of the epidemic — spread through returning migrants and long-distance transport routes.
▪ Rural PLHIV face longer distances to ART centres, greater stigma and higher rates of loss to follow-up.
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Route of transmission |
Approximate share of infections in India |
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Heterosexual (unprotected sex) |
~85–88% — by far the commonest route [VERY HIGH-YIELD] |
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Parent-to-child transmission |
~3–4% |
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Infected blood and blood products |
~1% |
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Injecting drug use (shared needles) |
~1.5–2% nationally; dominant in the north-east and Punjab |
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Homosexual / bisexual contact |
~1.5–2% |
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Unspecified / other |
Remainder |
▪ Approximately 60,000–70,000 children (< 15 years) living with HIV in India.
▪ Vertical transmission risk without any intervention: 15–45% (in-utero, intrapartum and via breastfeeding).
▪ With maternal ART, viral suppression and infant prophylaxis, transmission falls to < 1–2%. [VERY HIGH-YIELD]
▪ India follows a triple-elimination strategy — HIV, syphilis and hepatitis B vertical transmission.
▪ HIV–tuberculosis: TB is the commonest opportunistic infection and the leading cause of death in Indian PLHIV; ~3–5% of notified TB patients are HIV-positive; single-window "cross-referral" between NACO and NTEP is mandatory. [VERY HIGH-YIELD]
▪ HIV–HBV: ~2–9% of Indian PLHIV are HBsAg positive; ART must contain tenofovir + lamivudine (dual HBV-active agents).
▪ HIV–HCV: ~2–5% overall, but > 40–90% among people who inject drugs; curable with direct-acting antivirals.
▪ HIV Sentinel Surveillance (HSS) — biennial, unlinked anonymous testing at ANC clinics (general population proxy) and at targeted-intervention sites (key populations).
▪ HIV Estimations — biennial modelled national and state estimates (NACO with NIMS/ICMR and UNAIDS).
▪ Integrated Biological and Behavioural Surveillance (IBBS) — behavioural plus biological data in key populations.
▪ Strategic Information Management System (SIMS) — routine programme data from ICTCs, ART centres and targeted interventions.
▪ IDSP / IHIP — Integrated Disease Surveillance Programme and its digital Integrated Health Information Platform, for syndromic and outbreak surveillance.
▪ Nikshay — national TB information system, used for HIV–TB cross-notification.
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Population |
HIV prevalence in India (approximate) |
Key drivers |
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Female sex workers (FSW) |
~1.6–1.9% |
Multiple partners, inconsistent condom use, violence, STIs |
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Men who have sex with men (MSM) |
~3.3–4.3% |
Receptive anal intercourse, stigma, hidden networks |
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Transgender persons / Hijra |
~3.1–3.8% |
Sex work, marginalisation, violence, poor healthcare access |
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People who inject drugs (PWID) |
~6.3–9% — highest |
Shared needles and syringes; north-east and Punjab |
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Prison populations |
Elevated |
Pre-existing risk, drug use, unsafe sex, tattooing |
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Migrant workers |
~0.5–1% |
Separation from family, paid sex, low literacy, mobility |
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Long-distance truck drivers |
~0.9–1.2% |
Prolonged absence, roadside sex work, alcohol |
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Partners/spouses of PLHIV |
Elevated |
Serodiscordance, non-disclosure, non-use of condoms |
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Adolescents (10–19 years) |
Rising concern |
Early sexual debut, poor knowledge, abuse, substance use |
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Survivors of sexual assault |
Exposure risk |
Mucosal trauma, unknown source status — need PEP |
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Healthcare workers |
Occupational risk |
Needlestick and mucosal exposure — need PEP |
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High-Yield Ranking of Prevalence in Indian Key Populations PWID > MSM > Transgender > FSW > Truckers > Migrants > General population PWID have the highest HIV prevalence among Indian key populations. [FAVORITE EXAM QUESTION] |
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▪ Poverty — transactional sex, poor nutrition, inability to access or continue care.
▪ Stigma — the single greatest barrier to testing, disclosure and adherence; may be enacted, anticipated or internalised.
▪ Discrimination — in healthcare, employment, education, insurance and housing; prohibited under the HIV/AIDS Act 2017.
▪ Gender inequality — limited negotiating power for safer sex, economic dependence, early marriage.
▪ Sexual violence — forced sex causes mucosal trauma and precludes protection; also blocks disclosure and care-seeking.
▪ Migration — separation from family, anonymity, paid sex, discontinuity of ART across states.
▪ Conflict and displacement — collapse of health services, sexual violence, disrupted drug supply.
▪ Limited access to healthcare — distance, out-of-pocket costs, wage loss, absent adolescent-friendly services.
▪ Treatment interruption — driven by all of the above; the commonest cause of virological failure and resistance. [IMPORTANT]
▪ NACP-I (1992–1999): awareness, blood safety, surveillance.
▪ NACP-II (1999–2006): targeted interventions in key populations; decentralisation to State AIDS Control Societies.
▪ NACP-III (2007–2012): universal access to prevention, care and treatment; scale-up of ICTCs and ART centres.
▪ NACP-IV (2012–2017/2021): consolidation, "Treat All", elimination of parent-to-child transmission.
▪ NACP-V (2021–2026): attainment of 95-95-95, elimination of vertical transmission, and elimination of AIDS as a public-health threat by 2030.
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Body / facility |
Role |
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NACO (National AIDS Control Organisation) |
Apex body under the Ministry of Health and Family Welfare; policy, guidelines, drug procurement |
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SACS (State AIDS Control Societies) |
State-level implementation, monitoring and fund flow |
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DAPCU |
District AIDS Prevention and Control Units in high-burden districts |
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ICTC |
Integrated Counselling and Testing Centre — counselling, HIV testing, linkage to care |
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F-ICTC / PPP-ICTC |
Facility-integrated and public–private ICTCs extending testing to PHC level |
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ART Centre |
Initiation and monitoring of ART, CD4/viral-load testing, OI management |
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Link ART Centre (LAC) / LAC-Plus |
Peripheral drug refill and follow-up closer to the patient's home |
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Centre of Excellence (CoE) / ART Plus centre |
Second- and third-line ART, complex cases, training |
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Community Care Centre (CCC) |
Short-stay care, OI management, adherence and psychosocial support |
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PPTCT services |
Prevention of parent-to-child transmission — maternal testing, ART, infant prophylaxis and EID |
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Targeted Interventions (TI) |
NGO-led prevention packages for key populations — condoms, STI care, needle-syringe, OST |
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Blood-safety programme |
Licensed blood banks, mandatory screening (HIV, HBV, HCV, syphilis, malaria), NAT in select centres |
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Care, Support and Treatment (CST) division |
Free ART, OI drugs, nutrition and social-protection linkage |
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India-Specific Programme Essentials [VERY HIGH-YIELD] ▪ ART is free at all government ART centres under NACP. ▪ First-line adult regimen: TLD — Tenofovir + Lamivudine + Dolutegravir, one fixed-dose tablet once daily. ▪ HIV and AIDS (Prevention and Control) Act, 2017 — prohibits discrimination, mandates informed consent and confidentiality, requires an Ombudsman in every state. ▪ Testing must follow the three Cs: Consent, Confidentiality, Counselling. ▪ No person may be compelled to disclose HIV status; disclosure of a partner is permitted only by court order or with counselling-based consent. ▪ HIV–TB collaboration is mandatory: every TB patient tested for HIV (Nikshay) and every PLHIV screened for TB at every visit. |
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▪ Family: Retroviridae — RNA viruses that replicate through a DNA intermediate using reverse transcriptase.
▪ Subfamily: Orthoretrovirinae.
▪ Genus: Lentivirus — "slow viruses" causing chronic infection with long incubation. [COMMON MCQ]
▪ Species: Human immunodeficiency virus 1 and 2.
▪ Distinguishing features of lentiviruses: infect non-dividing cells (macrophages), persistent viraemia, gradual immune destruction, neurotropism.
HIV is a spherical, enveloped virus of 100–120 nm with a characteristic cone-shaped (truncated conical) nucleocapsid core on electron microscopy. [FAVORITE EXAM QUESTION]
|
Component |
Protein / gene product |
Function |
|
|
Lipid envelope |
Host cell-derived plasma membrane |
Outer coat; contains host MHC molecules; makes HIV fragile outside the body |
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gp120 |
Surface (SU) glycoprotein — env |
Binds CD4 receptor and chemokine coreceptor; heavily glycosylated "glycan shield" |
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gp41 |
Transmembrane (TM) glycoprotein — env |
Anchors gp120; mediates membrane fusion via its fusion peptide |
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p17 |
Matrix protein — gag |
Lines the inner envelope; targets pre-integration complex to the nucleus |
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p24 |
Capsid protein — gag |
Forms the conical core; major serological marker of early infection [VERY HIGH-YIELD] |
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p7 (p6/p7) |
Nucleocapsid — gag |
Binds and protects the genomic RNA |
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Genome |
Two identical copies of positive-sense ssRNA (~9.7 kb) |
Diploid genome — allows recombination |
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Reverse transcriptase (p66/p51) |
pol |
RNA-dependent DNA polymerase + RNase H; error-prone |
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Integrase (p32) |
pol |
Integrates proviral DNA into host chromosome |
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Protease (p10) |
pol |
Cleaves gag-pol polyprotein during maturation |
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Structural Pearls ▪ HIV carries three enzymes in the virion: reverse transcriptase, integrase, protease — targets of three drug classes. ▪ HIV is a diploid virus (two RNA copies) — the basis of recombination and subtype mixing. ▪ The envelope is host-derived → HIV is readily inactivated by heat, drying, alcohol, hypochlorite and detergents. ▪ gp120 + gp41 = gp160 precursor, cleaved by host furin. [COMMON MCQ] |
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▪ The genome is flanked by long terminal repeats (LTRs) containing promoter, enhancer and TATA elements that drive transcription.
▪ Nine genes in three functional categories: structural, regulatory and accessory.
|
Gene |
Products |
Function |
|
gag |
p24 (capsid), p17 (matrix), p7 (nucleocapsid), p6 |
Core structural proteins — "Group-specific AntiGen" |
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pol |
Reverse transcriptase, integrase, protease |
Viral enzymes; most conserved gene |
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env |
gp160 → gp120 + gp41 |
Envelope glycoproteins; most variable gene — hypervariable V1–V5 loops |
▪ tat (trans-activator of transcription) — binds the TAR element in the LTR and increases transcription > 1000-fold; without Tat, transcription aborts prematurely. [VERY HIGH-YIELD]
▪ rev (regulator of virion expression) — binds the RRE in env mRNA and exports unspliced and singly spliced viral RNA from nucleus to cytoplasm; the "early-to-late" switch.
|
Gene |
Principal function |
|
|
nef (negative factor) |
Downregulates CD4 and MHC class I on the infected cell → immune evasion from CTLs; enhances infectivity and virulence. Nef-deleted virus → attenuated infection. [FAVORITE EXAM QUESTION] |
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vif (viral infectivity factor) |
Degrades host restriction factor APOBEC3G, preventing lethal hypermutation of viral DNA |
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vpr (viral protein R) |
Nuclear import of the pre-integration complex into non-dividing cells; arrests the cell in G2; mild transactivator |
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vpu (viral protein U) |
HIV-1 only. Degrades CD4 in the ER and antagonises tetherin (BST-2) → efficient virion release |
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vpx (viral protein X) |
HIV-2 and SIV only. Degrades SAMHD1, permitting infection of macrophages and dendritic cells |
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Gene Mnemonic Structural: GAG–POL–ENV · Regulatory: Tat + Rev · Accessory: Nef, Vif, Vpr, Vpu (HIV-1), Vpx (HIV-2) "Vpu is Unique to HIV-1; Vpx is eXclusive to HIV-2" [VERY HIGH-YIELD] |
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▪ gp120 attachment to CD4 — the initiating event; triggers conformational change exposing the coreceptor-binding site.
▪ gp41 membrane fusion — insertion of the fusion peptide and formation of a six-helix bundle drawing the membranes together.
▪ Reverse transcription — RT converts ssRNA into double-stranded proviral DNA; RNase H degrades the RNA template.
▪ Integration — integrase inserts proviral DNA into host chromatin, preferentially into actively transcribed genes.
▪ Viral transcription — host RNA polymerase II acting on the LTR, greatly amplified by Tat.
▪ RNA transport — Rev exports unspliced/partially spliced transcripts for structural protein synthesis and genome packaging.
▪ Viral protein cleavage — protease cleaves Gag and Gag-Pol polyproteins during maturation; without it, virions are non-infectious.
▪ Immune evasion — Nef (CD4/MHC-I downregulation), glycan shielding of gp120, rapid antigenic variation, latency.
▪ Protection from APOBEC proteins — Vif targets APOBEC3G for proteasomal degradation.
▪ Viral budding — p6 recruits the host ESCRT machinery; Vpu neutralises tetherin to allow virion release.
▪ CD4 — the primary receptor; a member of the immunoglobulin superfamily present on helper T cells, monocytes/macrophages, dendritic cells and microglia. [VERY HIGH-YIELD]
▪ CCR5 — chemokine coreceptor used by R5-tropic (macrophage-tropic) virus; dominant in early and transmitted infection.
▪ CXCR4 — coreceptor used by X4-tropic (T-cell-tropic) virus; emerges late, associated with syncytium formation and accelerated CD4 decline.
▪ Dual/mixed-tropic virus — able to use both coreceptors.
▪ Dendritic-cell receptor DC-SIGN — binds gp120 without productive infection and carries virus (trans-infection) to lymph-node CD4 cells.
|
CCR5-Δ32 Mutation [FAVORITE EXAM QUESTION] ▪ A 32-base-pair deletion in the CCR5 gene produces a non-functional coreceptor. ▪ Homozygotes (Δ32/Δ32) — near-complete resistance to R5-tropic HIV infection; ~1% of Northern Europeans; essentially absent in Indians. ▪ Heterozygotes — partial protection, lower viral set point and slower progression. ▪ Basis of the "Berlin patient" and "London patient" cures by allogeneic stem-cell transplantation from CCR5-Δ32 donors. ▪ Basis of the drug maraviroc, a CCR5 antagonist. |
▪ Coreceptor tropism testing (genotypic V3-loop or phenotypic Trofile assay) is mandatory before using maraviroc — it works only against R5-tropic virus. [IMPORTANT]
|
HIV Replication Cycle — Stepwise (with Drug Targets) 1. Attachment — gp120 binds CD4 [Attachment inhibitor: fostemsavir] ↓ 2. Coreceptor binding — gp120 binds CCR5 or CXCR4 [CCR5 antagonist: maraviroc] ↓ 3. Fusion — gp41 fusion peptide merges viral and cell membranes [Fusion inhibitor: enfuvirtide] ↓ 4. Uncoating — capsid core released into cytoplasm [Capsid inhibitor: lenacapavir] ↓ 5. Reverse transcription — ssRNA → dsDNA [NRTIs, NtRTIs, NNRTIs] ↓ 6. Formation of proviral DNA and pre-integration complex; nuclear import (Vpr, p17) ↓ 7. Integration — integrase inserts provirus into host genome [INSTIs: dolutegravir, bictegravir, raltegravir] ↓ 8. Transcription — host RNA Pol II at the LTR, amplified by Tat ↓ 9. Translation — Gag, Gag-Pol and Env polyproteins synthesised; Rev exports RNA ↓ 10. Assembly — polyproteins and two genomic RNA copies assemble at the plasma membrane ↓ 11. Budding — release via ESCRT machinery; Vpu antagonises tetherin ↓ 12. Maturation — protease cleaves polyproteins → infectious virion [Protease inhibitors] |
|
|
Replication-Cycle Pearls ▪ Integration is the irreversible step — once integrated, the provirus persists for the life of the cell. [VERY HIGH-YIELD] ▪ Protease acts at maturation, not entry — PI-treated virions bud but are non-infectious. ▪ Reverse transcriptase lacks proofreading (no 3'→5' exonuclease) → ~1 error per genome per cycle → resistance and quasispecies. ▪ Post-attachment inhibitor: ibalizumab (anti-CD4 monoclonal) blocks step 2–3. |
|
▪ High viral turnover: ~10 billion (10¹⁰) virions produced daily; plasma virion half-life ~6 hours; infected CD4 cell half-life ~1.6 days.
▪ Error-prone reverse transcriptase: mutation rate ~3 × 10⁻⁵ per base per cycle → every possible single point mutation arises daily. [VERY HIGH-YIELD]
▪ Quasispecies: the swarm of genetically related but distinct variants within one host; the substrate for rapid drug-resistance selection.
▪ Viral set point: the stable plasma viral load reached ~6 months after seroconversion; the strongest single predictor of rate of progression. [FAVORITE EXAM QUESTION]
▪ Latently infected resting memory CD4+ T cells — the principal reservoir; transcriptionally silent, invisible to immune surveillance and unaffected by ART; half-life ~44 months, requiring > 60 years of ART to decay.
▪ Tissue sanctuary sites: central nervous system (microglia, perivascular macrophages), gut-associated lymphoid tissue, lymph nodes, genital tract, testes — sites of poor drug penetration.
▪ Macrophage and follicular dendritic cell reservoirs — long-lived, relatively resistant to cytopathic effect.
▪ Clonal expansion of infected cells — homeostatic and antigen-driven proliferation replenishes the reservoir without new rounds of replication.
|
Why HIV Cannot Yet Be Cured [IMPORTANT] ▪ Integration into the host genome makes the provirus a permanent part of the cell. ▪ Latency — silent provirus is not targeted by ART (which acts only on replicating virus) or by the immune system. ▪ Sanctuary sites with poor drug penetration allow ongoing low-level replication. ▪ Clonal expansion of infected cells maintains reservoir size. ▪ Extreme genetic variability defeats immune control and complicates vaccine design. Strategies under study: "shock and kill" (latency-reversing agents), "block and lock", gene editing of CCR5, broadly neutralising antibodies, therapeutic vaccines. |
|
Exposure |
Estimated risk per exposure |
|
Blood transfusion (infected unit) |
~90–95% — highest of all routes [VERY HIGH-YIELD] |
|
Vertical transmission, no intervention |
15–45% |
|
Receptive anal intercourse |
~1.4% (1 in 70) |
|
Needle sharing (injecting drug use) |
~0.6–0.8% (1 in 150) |
|
Percutaneous needlestick injury |
~0.3% (1 in 300) [COMMON MCQ] |
|
Insertive anal intercourse |
~0.11% |
|
Receptive vaginal intercourse |
~0.08% (1 in 1250) |
|
Insertive vaginal intercourse |
~0.04% |
|
Mucous-membrane splash exposure |
~0.09% (1 in 1000) |
|
Receptive oral sex |
< 0.01% — very low but not zero |
|
Intact skin exposure |
Negligible |
▪ Heterosexual transmission is the commonest route worldwide and accounts for ~85–88% of infections in India. [VERY HIGH-YIELD]
▪ Male-to-male (MSM) transmission — high per-act risk, chiefly through receptive anal intercourse; a growing share of new infections in urban India.
▪ Receptive intercourse carries far higher risk than insertive intercourse because of the large, thin, highly vascular rectal/vaginal mucosal surface and abundant target cells.
▪ Male-to-female transmission is ~2–3 times more efficient than female-to-male, due to larger mucosal exposure area and prolonged contact with semen. [COMMON MCQ]
▪ Genital mucosal injury — trauma, dry sex, forced intercourse, obstetric injury.
▪ Genital ulcer disease — herpes simplex-2, syphilis, chancroid; increase risk 2–5 fold by breaching the epithelium and recruiting activated CD4 cells. [VERY HIGH-YIELD]
▪ Other STIs — gonorrhoea, chlamydia, trichomoniasis, bacterial vaginosis increase both susceptibility and infectiousness.
▪ High plasma viral load — the strongest single determinant; risk rises ~2.5 fold per log₁₀ increase.
▪ Genital viral shedding — may be discordant with plasma levels, especially with concurrent STIs.
▪ Acute HIV infection in the source — up to 26-fold higher transmission risk due to very high viraemia. [FAVORITE EXAM QUESTION]
▪ Cervical ectopy, menstruation, lack of male circumcision, concurrent partnerships and alcohol/substance use.
▪ Consistent correct condom use — ~80–95% risk reduction.
▪ Voluntary medical male circumcision — ~60% reduction in female-to-male transmission (removes keratin-poor, Langerhans-cell-rich inner foreskin).
▪ Treatment as prevention (TasP) — ART for the index partner; HPTN 052 showed a 96% reduction in linked transmission. [VERY HIGH-YIELD]
▪ U = U (Undetectable = Untransmittable) — no sexual transmission has been documented from a person with sustained HIV RNA < 200 copies/mL (PARTNER, PARTNER-2, Opposites Attract studies).
▪ PrEP for the negative partner; prompt STI diagnosis and treatment.
▪ Blood transfusion — highest per-exposure risk (~90–95%); now rare where mandatory screening and NAT are used.
▪ Blood products — clotting factor concentrates (historically devastating for haemophiliacs); modern heat/solvent-detergent treatment has eliminated this risk. Albumin and immunoglobulins have never transmitted HIV.
▪ Shared injecting equipment — needles, syringes, cookers, cotton filters and rinse water; the dominant route in north-east India and Punjab.
▪ Unsafe injections — reuse of needles/syringes in informal healthcare settings.
▪ Contaminated surgical and dental instruments — inadequate sterilisation.
▪ Tattooing, body piercing, ear piercing, shaving by barbers, ritual scarification — theoretical to low risk with shared unsterilised equipment.
▪ Organ and tissue transplantation and artificial insemination with unscreened donor material.
|
Window-Period Transfusion Risk ▪ Screening detects antibody/antigen but not infections within the window period. ▪ Nucleic acid testing (NAT) shortens the window to ~5–10 days and reduces residual risk to <1 in a million units. ▪ India: NAT is not yet universally mandatory; ELISA/rapid test screening for HIV, HBV, HCV, syphilis and malaria is mandatory in all licensed blood banks. [IMPORTANT] |
|
Timing |
Approximate contribution (untreated) |
|
Intrauterine (in utero) — transplacental, mainly third trimester |
~5–10% |
|
Intrapartum — exposure to maternal blood and genital secretions during delivery |
~10–20% — the largest single component [VERY HIGH-YIELD] |
|
Postnatal — breastfeeding |
~5–20% (cumulative, related to duration) |
▪ High maternal viral load — the single most important determinant; risk is very low if RNA < 50 copies/mL.
▪ Absent or late maternal ART; poor adherence; acute HIV infection during pregnancy or lactation.
▪ Low maternal CD4 count and advanced disease.
▪ Prolonged rupture of membranes (> 4 hours) — risk rises ~2% per additional hour. [COMMON MCQ]
▪ Obstetric procedures — invasive fetal monitoring, episiotomy, instrumental delivery, amniocentesis, chorionic villus sampling.
▪ Prematurity and low birth weight — immature skin and immune barriers.
▪ Chorioamnionitis and untreated genital infections.
▪ Mixed feeding — combining breast milk with other feeds damages gut mucosa and carries higher risk than exclusive breastfeeding. [VERY HIGH-YIELD]
▪ Cracked nipples, mastitis, breast abscess and infant oral thrush.
▪ Needlestick injury — average risk 0.3%; the commonest occupational exposure.
▪ Mucous-membrane exposure — risk ~0.09%.
▪ Non-intact skin exposure — risk < 0.1%; intact skin is an effective barrier.
▪ Deep injury (the strongest determinant).
▪ Hollow-bore needle rather than solid suture needle.
▪ Visibly blood-stained device.
▪ Needle previously placed in the source patient's artery or vein.
▪ High source viral load (e.g. acute infection or terminal AIDS).
▪ Absence of gloves; large volume of inoculum. [COMMON MCQ]
|
Management of Occupational Exposure Sharps injury or mucosal splash ↓ Immediate first aid — do NOT squeeze or scrub; wash with soap and running water; irrigate mucosa/eyes with saline or water; no bleach or caustics ↓ Report immediately to the designated PEP officer / nodal officer ↓ Exposure-risk categorisation and source-patient evaluation (HIV, HBsAg, anti-HCV with consent) ↓ Baseline testing of exposed worker — HIV, HBsAg, anti-HBs, anti-HCV, LFT, RFT, pregnancy test ↓ Start PEP within 2 hours (ideally), always < 72 hours — TDF + 3TC + DTG for 28 days ↓ Counselling; safe sex and no blood/organ donation for 3 months ↓ Follow-up HIV testing at 6 weeks, 3 months and 6 months |
▪ Definitely infectious (high risk): blood, semen, vaginal secretions, rectal secretions, breast milk.
▪ Potentially infectious (universal precautions apply): cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid.
▪ Any body fluid visibly contaminated with blood, and unfixed tissues, organs and laboratory virus preparations.
▪ Saliva — contains inhibitory proteins (secretory leukocyte protease inhibitor, thrombospondin); transmission by kissing has essentially never been documented (except a single case with severe oral bleeding).
▪ Sweat, tears, nasal secretions, sputum, vomitus.
▪ Urine without visible blood and faeces without visible blood.
|
High-Yield Memory Aid "BBSVR" fluids transmit HIV — Blood, Breast milk, Semen, Vaginal secretions, Rectal secretions. "STUFS" fluids do not — Saliva, Tears, Urine, Faeces, Sweat (unless visibly bloodstained). [FAVORITE EXAM QUESTION] |
▪ Casual social contact, hugging, handshakes, touching.
▪ Sharing utensils, plates, cups, food or drink.
▪ Sharing toilets, bathrooms, bed linen or clothing.
▪ Swimming pools, public transport, workplaces and schools.
▪ Mosquito and other insect bites — HIV does not replicate in insects and there is no regurgitation of blood. [VERY HIGH-YIELD]
▪ Coughing, sneezing, air-borne or droplet spread.
▪ Donating blood using sterile disposable equipment.
|
Counselling Point Clear communication that HIV is not spread by casual contact is the single most effective clinical intervention against stigma, and is explicitly protected under the HIV and AIDS (Prevention and Control) Act, 2017, which prohibits discrimination in employment, education, housing and healthcare. |
|
Early Pathogenesis — First 2 Weeks Mucosal entry — virus crosses genital/rectal epithelium through microabrasions, or is transcytosed / captured by Langerhans and dendritic cells ↓ Founder virus — a single (or very few) transmitted/founder variant establishes infection; almost always R5-tropic ↓ Infection of mucosal CD4 cells — resting and activated CD4 T cells in the lamina propria ↓ Dendritic-cell transport via DC-SIGN to the draining lymph node (trans-infection) ↓ Regional lymph-node amplification — explosive replication in the CD4-rich paracortex ↓ Systemic viraemia (day 10–21) — peak plasma HIV RNA often > 10⁶–10⁷ copies/mL ↓ Dissemination to all lymphoid tissue, CNS and genital tract; reservoir established within days ↓ Massive depletion of gut-associated lymphoid tissue (GALT) CD4 cells — up to 60–80% lost in the first weeks |
|
|
Critical Concept — GALT Depletion [VERY HIGH-YIELD] ▪ The gut contains the largest pool of CD4 T cells in the body, most being CCR5-high, activated memory cells — the ideal HIV target. ▪ Massive, largely irreversible GALT CD4 depletion occurs in the first 2–4 weeks, long before peripheral blood CD4 falls appreciably. ▪ Loss of the mucosal barrier permits microbial translocation (circulating LPS, bacterial DNA) → chronic immune activation → accelerated CD4 loss and non-AIDS comorbidities. ▪ This is why the "eclipse and early window" is the only realistic period for a functional cure and why very early ART limits reservoir size. |
|
|
Mechanism |
Explanation |
|
Direct viral cytopathic effect |
Budding damages the membrane; accumulation of unintegrated DNA and viral proteins kills productively infected cells |
|
Syncytium formation |
gp120 on an infected cell binds CD4 on uninfected cells → multinucleated giant cells; characteristic of X4-tropic virus |
|
Apoptosis |
Programmed death of infected and bystander cells, driven by gp120, Tat, Nef, Vpr and chronic activation |
|
Pyroptosis |
Caspase-1-mediated inflammatory death of abortively infected resting CD4 cells — accounts for > 95% of CD4 death; releases IL-1β and amplifies inflammation [FAVORITE EXAM QUESTION] |
|
Immune-mediated killing |
CTL lysis of infected cells; antibody-dependent cellular cytotoxicity; innocent-bystander killing of cells coated with gp120 |
|
Thymic dysfunction |
Direct infection of thymocytes and thymic stroma reduces output of naïve CD4 cells |
|
Impaired regeneration |
Reduced IL-7 responsiveness; exhaustion of the naïve pool |
|
Lymphoid tissue fibrosis |
Collagen deposition in T-cell zones destroys the fibroblastic reticular network and IL-7 survival niches — a key reason for poor CD4 recovery despite viral suppression |
|
Chronic immune activation |
Persistent activation drives cells into an activated, short-lived, apoptosis-prone state and depletes the regenerative reserve |
▪ Progressive CD4 depletion — untreated fall of ~50–80 cells/µL/year; loss of helper function for both cellular and humoral immunity.
▪ Preferential loss of Th17 cells in gut mucosa → impaired mucosal antibacterial/antifungal defence.
▪ CD8 T-cell exhaustion — sustained antigen exposure upregulates PD-1, CTLA-4, TIM-3 and LAG-3; CTLs lose proliferative and cytotoxic capacity.
▪ B-cell dysregulation — polyclonal activation, exhausted/tissue-like memory B cells, poor vaccine responses.
▪ Polyclonal hypergammaglobulinaemia with paradoxically poor specific antibody responses → recurrent pneumococcal and other encapsulated bacterial infections, especially in children. [IMPORTANT]
▪ Monocyte and macrophage dysfunction — impaired chemotaxis, phagocytosis and intracellular killing; macrophages act as reservoirs and disseminate virus to the CNS.
▪ Dendritic-cell dysfunction — reduced numbers, impaired antigen presentation; plasmacytoid DCs produce excess type-I interferon driving activation.
▪ Natural-killer-cell dysfunction — expansion of anergic CD56-negative NK cells with reduced cytotoxicity.
▪ Loss of mucosal immunity — GALT destruction, loss of Th17 and secretory IgA.
▪ Microbial translocation — LPS and bacterial products cross the damaged gut into the portal and systemic circulation.
▪ Persistent inflammation — raised IL-6, D-dimer, hsCRP and sCD14 predict cardiovascular events, malignancy and all-cause mortality even on suppressive ART.
▪ Immune senescence — accumulation of CD28-negative, CD57-positive terminally differentiated cells; telomere shortening → "accelerated ageing" phenotype.
▪ Latent reservoirs established within days of infection and never eliminated by ART.
▪ Resting memory CD4 cells — chiefly central and transitional memory subsets; the dominant and best-characterised reservoir.
▪ Macrophage reservoirs — long-lived, relatively resistant to cytopathic effect; important in lung and CNS.
▪ CNS reservoirs — microglia and perivascular macrophages behind the blood–brain barrier; a site of independent viral evolution ("CSF escape").
▪ Lymphoid-tissue reservoirs — follicular dendritic cells trap virions on their surface as immune complexes; B-cell follicles largely exclude CD8 CTLs.
▪ Sanctuary sites — CNS, testes, genital tract, gut — sub-therapeutic drug concentrations permit low-level replication.
▪ Integration into the host genome — the fundamental obstacle; integration into transcriptionally silent chromatin favours latency, while clonal expansion of cells with intact proviruses replenishes the reservoir.
|
Stage |
Timing |
Key features |
|
|
Eclipse phase |
Day 0–10 |
Virus replicating in mucosa and lymph node; all blood tests negative — the true window period |
|
|
Acute viraemic phase |
Week 2–4 |
Explosive viraemia; p24 antigen and HIV RNA detectable; transient CD4 fall |
|
|
Acute retroviral syndrome |
Week 2–6 |
Fever, rash, pharyngitis, lymphadenopathy in 50–90%; often mistaken for dengue or infectious mononucleosis |
|
|
Seroconversion |
Week 3–12 |
HIV antibodies appear; viraemia falls sharply as CTL responses develop |
|
|
Early chronic infection |
Month 3–6 |
Viral set point established; CD4 partially recovers |
|
|
Clinical latency |
Median 8–10 years |
Asymptomatic or PGL; continuous high-level replication in lymphoid tissue; CD4 falls ~50–80/µL/year |
|
|
Symptomatic chronic HIV |
CD4 200–350 |
TB, oral candidiasis, herpes zoster, weight loss, chronic diarrhoea (WHO stage 2–3) |
|
|
Advanced HIV disease |
CD4 < 200 |
AIDS-defining opportunistic infections and malignancies |
|
|
AIDS |
Terminal |
Untreated median survival after AIDS ≈ 1–2 years |
|
|
The Word "Latency" Is Misleading [IMPORTANT] Clinical latency ≠ viral latency. During the asymptomatic phase the virus replicates continuously and at high level in lymphoid tissue — roughly 10¹⁰ virions and 10⁹ CD4 cells are produced and destroyed daily. The patient is well only because production temporarily balances destruction. |
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|
Sequence of Laboratory Marker Appearance [FAVORITE EXAM QUESTION] HIV RNA — detectable from day ~10 (earliest marker) ↓ p24 antigen — detectable from day ~14–16 ↓ IgM antibody (3rd-generation assay) — day ~20–25 ↓ IgG antibody (2nd-generation assay) — day ~25–35 ↓ Western blot / line immunoassay fully reactive — week 4–6 ↓ Note: p24 antigen disappears (drops below detection) once antibody appears — the classic "p24 window/dip" |
▪ Peak viraemia at 3–6 weeks; often > 10⁶–10⁷ copies/mL, with maximal infectiousness.
▪ Viral set point established by month 6: set point > 100,000 copies/mL predicts rapid progression; < 10,000 predicts slow progression. [VERY HIGH-YIELD]
▪ Gradual CD4 decline thereafter; risk of specific opportunistic infections tracks the CD4 threshold.
▪ Progression to opportunistic infections accelerates once CD4 falls below 200 cells/µL.
▪ Effect of ART: viral load falls ~1 log₁₀ by week 4 and becomes undetectable by 12–24 weeks; CD4 rises rapidly by ~50–100 cells/µL in the first 3 months (redistribution), then ~50–100 cells/µL per year (true regeneration).
|
Pattern |
Proportion |
Characteristics |
|
Typical progressors |
~80–85% |
AIDS within a median of 8–10 years without ART |
|
Rapid progressors |
~10% |
AIDS within 2–3 years; high set point; often X4 virus early; poor CTL response |
|
Long-term non-progressors |
~5% |
CD4 > 500 and asymptomatic beyond 7–10 years without ART |
|
Elite controllers |
~0.5% |
HIV RNA < 50 copies/mL without ART; strongly associated with HLA-B*57:01 and HLA-B*27; still show chronic immune activation and excess cardiovascular risk |
|
HIV-2 progression |
— |
Markedly slower; many never progress; lower viral loads and reduced transmissibility |
▪ Viral set point — the strongest virological predictor. [VERY HIGH-YIELD]
▪ CD4 count — the strongest immunological predictor and the basis of OI prophylaxis decisions.
▪ Age — progression is faster in infants (bimodal paediatric course) and in adults over 40 years.
▪ Coinfections — tuberculosis, HBV, HCV, CMV, malaria and helminths raise immune activation and viral load.
▪ Host genetics — protective: HLA-B*57:01, HLA-B*27, CCR5-Δ32 heterozygosity; deleterious: HLA-B*35, CCR5 promoter variants; HLA class I homozygosity accelerates progression.
▪ Adherence to ART — the single most powerful modifiable determinant of outcome. [IMPORTANT]
▪ Nutritional status — low BMI, micronutrient deficiency and anaemia predict mortality; particularly relevant in Indian cohorts.
▪ Substance use — alcohol, injecting drugs and tobacco worsen adherence, immune function and comorbidity risk.
▪ Others: high plasma markers of inflammation (IL-6, sCD14, D-dimer), low haemoglobin, and X4 coreceptor switch.
Acute (primary) HIV infection is the phase between acquisition of the virus and the completion of seroconversion, characterised by very high viraemia, detectable p24 antigen and HIV RNA, and incomplete or absent antibody response.
▪ Timing after exposure: symptoms appear 2–4 weeks (range 1–6 weeks) after acquisition and last 1–3 weeks.
▪ Acute retroviral syndrome (ARS) — the symptomatic form; occurs in 50–90% of newly infected persons but is recognised in far fewer because it mimics common viral illnesses. [VERY HIGH-YIELD]
▪ Asymptomatic acute infection — a substantial minority have no symptoms at all and are diagnosed only incidentally.
▪ Very high viral load (often > 10⁶–10⁷ copies/mL) makes this the phase of maximal infectiousness — up to 26-fold higher transmission risk per act. [FAVORITE EXAM QUESTION]
▪ Acute infection contributes disproportionately (up to 30–50%) to onward transmission in some epidemics.
▪ Fever — the commonest feature (~75–90%); usually low-to-moderate grade.
▪ Generalised lymphadenopathy — symmetrical, non-tender, especially cervical, axillary and occipital.
▪ Pharyngitis — sore throat, typically non-exudative with mucosal erythema (contrast with streptococcal exudate).
▪ Maculopapular rash (~40–70%) — non-pruritic, erythematous, 5–10 mm macules/papules on the trunk, face, palms and soles; appears 48–72 hours after fever onset. [VERY HIGH-YIELD]
▪ Myalgia and arthralgia; profound fatigue.
▪ Headache — often with retro-orbital pain and photophobia.
▪ Aseptic meningitis — lymphocytic CSF pleocytosis with normal glucose; HIV should be considered in any young adult with aseptic meningitis. [IMPORTANT]
▪ Encephalitis, myelitis, Guillain-Barré syndrome, brachial neuritis, facial palsy — rare neurological presentations.
▪ Painful mucocutaneous ulcers — shallow, well-circumscribed oral, oesophageal, genital or anal ulcers; highly suggestive of acute HIV. [FAVORITE EXAM QUESTION]
▪ Diarrhoea, nausea, vomiting, anorexia and weight loss.
▪ Hepatitis — transaminitis with or without hepatomegaly.
▪ Cytopenias — lymphopenia followed by lymphocytosis with atypical lymphocytes, thrombocytopenia, mild leucopenia.
▪ Oral candidiasis during acute infection indicates a profound transient CD4 dip and predicts rapid progression.
▪ Splenomegaly, night sweats, cough.
|
When to Suspect Acute HIV [VERY HIGH-YIELD] Suspect acute HIV in any patient with an undifferentiated febrile illness plus: ▪ Rash involving palms and soles, or ▪ Non-exudative pharyngitis with generalised lymphadenopathy, or ▪ Painful mucocutaneous ulcers, or ▪ Aseptic meningitis in a young adult, or ▪ A recent high-risk exposure — and always ask about exposure. A standard antibody test may be negative — order HIV RNA or a 4th-generation Ag/Ab assay. |
▪ HIV-1 RNA (viral load) — the earliest marker, positive from day ~10; levels are usually very high. A low-positive result (< 5000 copies/mL) may be a false positive and must be repeated. [VERY HIGH-YIELD]
▪ p24 antigen — positive from day ~14–16; disappears as antibody appears.
▪ Fourth-generation combined antigen/antibody assay — the recommended first-line test; detects infection from ~day 15–20.
▪ Repeat antibody testing at 4–6 weeks and 3 months to document seroconversion.
▪ CBC — lymphopenia then atypical lymphocytosis, thrombocytopenia.
▪ Liver function tests — mild-to-moderate transaminase elevation.
▪ CSF examination where indicated — lymphocytic pleocytosis, mildly raised protein, normal glucose; HIV RNA detectable in CSF.
▪ Baseline CD4 count (often transiently low — do not over-interpret), and baseline resistance genotype where available.
|
Condition |
Discriminating features |
|
EBV infectious mononucleosis |
Exudative tonsillitis, marked posterior cervical nodes, splenomegaly, positive Monospot/EBV VCA IgM; rash typically only after ampicillin |
|
CMV infection |
Fever with hepatitis and atypical lymphocytosis; CMV IgM/DNA positive; pharyngitis less prominent |
|
Secondary syphilis |
Rash on palms and soles, condylomata lata, painless prior chancre; VDRL/RPR and TPHA positive |
|
Viral hepatitis A/B/E |
Jaundice, marked transaminase elevation, positive hepatitis serology; rash uncommon |
|
Dengue |
India — severe myalgia, retro-orbital pain, thrombocytopenia, positive NS1/IgM; petechial rash [COMMON MCQ] |
|
Influenza / COVID-19 |
Prominent respiratory symptoms; positive antigen/RT-PCR; rash uncommon |
|
Drug eruption |
Temporal relation to a new drug; pruritus prominent; eosinophilia |
|
Streptococcal pharyngitis |
Exudative tonsils, tender anterior cervical nodes, absent cough; positive throat swab |
|
Others in Indian practice |
Enteric fever, scrub typhus, malaria, acute toxoplasmosis, rubella, measles, chikungunya |
▪ Immediate ART — start on the same day whenever possible; do not wait for confirmatory serology or CD4. [VERY HIGH-YIELD]
▪ Rationale for early ART: limits reservoir size, preserves GALT and CD4 function, lowers the set point, reduces the severity of ARS and prevents onward transmission.
▪ Baseline resistance testing — send genotype before starting, but do not delay ART while awaiting the result.
▪ Screening for coinfections — syphilis, gonorrhoea, chlamydia, HBV, HCV, tuberculosis.
▪ Partner testing and notification; index testing of family members.
▪ Prevention counselling — condoms, disclosure, U = U explained, PrEP for the negative partner.
▪ Follow-up viral load at 4 weeks, 12 weeks and 24 weeks to confirm suppression.
▪ Psychological support at diagnosis is essential — this is a period of high distress and suicide risk.
▪ Relationship of acute viral load to progression: a high peak and high set-point viral load, and symptomatic ARS lasting > 14 days, both predict faster progression.
▪ Effect of early ART: treatment within the first weeks (ideally within Fiebig stages I–II) markedly reduces the size of the latent reservoir and improves immune recovery.
▪ Reservoir formation begins within days of infection and cannot be fully prevented — this is why "cure" remains elusive even with immediate ART.
▪ Rare cases of post-treatment control ("VISCONTI cohort") followed very early ART, but remain exceptional.
▪ Date of HIV diagnosis and where it was made; previous HIV tests and their results.
▪ Probable route of acquisition — sexual, injecting drug use, transfusion, vertical, occupational.
▪ History suggestive of acute seroconversion illness and its approximate date.
▪ Previous opportunistic infections — which, when, treated how, completed or not.
▪ Previous tuberculosis — pulmonary or extrapulmonary, drug-sensitive or resistant, regimen, outcome, Nikshay ID.
▪ Previous AIDS-defining illnesses and lowest recorded (nadir) CD4 count.
▪ ART history — all regimens ever taken, dates, reasons for change.
▪ Adherence — missed doses in the last month, pill-taking routine, pharmacy refill record.
▪ Treatment interruptions — duration and reason (stock-out, migration, side effects, denial, alternative medicine).
▪ Virological failure episodes and any resistance testing results.
▪ Drug adverse effects experienced — rash, jaundice, neuropathy, renal, psychiatric.
▪ Concomitant medicines — especially rifampicin, anti-epileptics, antacids, calcium/iron, PPIs, statins, steroids, hormonal therapy.
▪ Herbal and alternative medicines — ayurvedic, siddha, homoeopathic preparations; St John's wort; may cause interactions and hepatotoxicity. [IMPORTANT]
▪ Allergies — particularly to sulfonamides, abacavir and nevirapine.
▪ Vaccination status — hepatitis B, pneumococcal, influenza, COVID-19, HPV, tetanus.
▪ Number and gender of partners; type of sexual practice; condom use and consistency.
▪ Contraception in use; fertility intention and pregnancy planning.
▪ Previous STIs — genital ulcers, discharge, warts, syphilis serology.
▪ Transactional sex, sexual violence or coercion.
▪ Injecting-drug use — substances, sharing of equipment, opioid-substitution therapy.
▪ Alcohol use — quantity, dependence (AUDIT-C), relevance to hepatotoxicity and adherence.
▪ Other substance use — tobacco, cannabis, stimulants.
▪ Transfusion history; occupational exposure history.
▪ Travel and environmental exposure — residence in histoplasmosis-endemic areas, kala-azar belt (Bihar, Jharkhand, West Bengal, eastern UP), penicilliosis/talaromycosis in north-east India and Southeast Asia, pets, birds, well water.
▪ Family and partner testing — spouse, children, other sexual partners (index testing).
▪ Pregnancy — current or planned; obstetric history.
▪ Mental health — depression, anxiety, sleep, adjustment disorder.
▪ Cognitive symptoms — forgetfulness, slowing, poor concentration.
▪ Suicidal ideation — must be asked directly, especially at diagnosis and at treatment failure. [IMPORTANT]
▪ Social support — family awareness, caregivers, peer/positive-network membership.
▪ Disclosure status — to whom disclosed; risks of unwanted disclosure.
▪ Stigma — experienced discrimination in healthcare, workplace or family.
▪ Employment, housing and food security — determinants of adherence and nutrition.
▪ Vital signs: temperature, pulse, blood pressure (supine and standing — adrenal insufficiency), respiratory rate, oxygen saturation at rest and after exertion (desaturation on exertion suggests Pneumocystis pneumonia). [VERY HIGH-YIELD]
▪ Anthropometry: weight at every visit, BMI, mid-upper arm circumference (MUAC) — MUAC < 19 cm in adults indicates severe acute malnutrition and predicts mortality.
▪ Pallor — anaemia of chronic disease, zidovudine, parvovirus B19, marrow infiltration.
▪ Icterus — drug-induced liver injury, viral hepatitis, atazanavir hyperbilirubinaemia.
▪ Cyanosis and clubbing — PCP, bronchiectasis, lymphocytic interstitial pneumonitis, chronic lung disease.
▪ Dehydration — chronic diarrhoea, adrenal insufficiency.
▪ Oedema — nephropathy, hypoalbuminaemia, cardiomyopathy, chronic liver disease.
▪ Cachexia and temporal wasting — HIV wasting syndrome, disseminated TB, malignancy.
▪ Generalised lymphadenopathy — record site, size, tenderness, matting, fluctuation; asymmetrical, matted or tender nodes suggest TB or lymphoma rather than PGL. [IMPORTANT]
▪ Parotid enlargement — diffuse infiltrative lymphocytosis syndrome (DILS), lymphoepithelial cysts (particularly in children).
▪ Lipodystrophy — the combination of peripheral lipoatrophy (face, limbs, buttocks; classically stavudine/zidovudine) and central adiposity (abdominal, dorsocervical "buffalo hump", breast enlargement).
▪ Gynaecomastia — efavirenz, hypogonadism, chronic liver disease.
▪ Injection marks / track marks — evidence of injecting drug use; look for thrombophlebitis and abscesses.
▪ Oral candidiasis — pseudomembranous (removable white plaques), erythematous, or angular cheilitis; a marker of CD4 < 200 and a predictor of oesophageal disease. [VERY HIGH-YIELD]
▪ Oral hairy leukoplakia — corrugated white plaques on the lateral tongue margin that cannot be scraped off; caused by Epstein-Barr virus; virtually pathognomonic of HIV. [FAVORITE EXAM QUESTION]
▪ Aphthous ulcers — recurrent, large, painful, often on non-keratinised mucosa; may respond to thalidomide.
▪ HSV ulcers — grouped vesicles progressing to shallow ulcers on keratinised mucosa; chronic (> 1 month) HSV ulcer is AIDS-defining.
▪ CMV ulcers — large, deep, painful, punched-out ulcers; require biopsy for diagnosis.
▪ Kaposi sarcoma — purple/red macules or nodules on the hard palate and gingiva.
▪ Necrotising ulcerative gingivitis and necrotising ulcerative periodontitis — rapid destruction of periodontal tissues with severe pain, halitosis and bone loss.
▪ Dental caries and linear gingival erythema.
▪ HPV lesions — oral warts, which paradoxically may increase after ART.
▪ Oral pigmentation — HIV itself, zidovudine, adrenal insufficiency.
▪ Salivary-gland enlargement and xerostomia — DILS; increases caries risk.
▪ Seborrhoeic dermatitis — greasy erythematous scaling of scalp, nasolabial folds, eyebrows, chest; extensive and refractory in HIV; associated with Malassezia.
▪ Pruritic papular eruption (PPE) — intensely itchy symmetrical papules on the extremities and trunk with post-inflammatory hyperpigmentation; very common in India and Africa and a marker of advanced immunosuppression. [VERY HIGH-YIELD]
▪ Xerosis and acquired ichthyosis — dry, scaly skin.
▪ Eosinophilic folliculitis — itchy follicular papules/pustules on the face and upper trunk, typically at CD4 < 250; may flare as IRIS.
▪ Scabies and crusted (Norwegian) scabies — hyperkeratotic crusted plaques teeming with mites; highly contagious; seen at very low CD4. [IMPORTANT]
▪ Extensive dermatophytosis — widespread tinea corporis, tinea unguium, proximal white subungual onychomycosis (suggestive of HIV).
▪ Molluscum contagiosum — multiple, large (> 1 cm "giant"), umbilicated facial lesions in adults suggest advanced HIV.
▪ Herpes simplex — chronic, extensive, ulcerative perianal/genital lesions.
▪ Herpes zoster — multidermatomal, recurrent or disseminated zoster; zoster in a young adult should prompt HIV testing. [COMMON MCQ]
▪ Bacillary angiomatosis — friable vascular papules/nodules due to Bartonella henselae/quintana; mimics Kaposi sarcoma.
▪ Kaposi sarcoma — violaceous macules, plaques and nodules following skin cleavage lines; HHV-8 related.
▪ Cutaneous cryptococcosis — umbilicated molluscum-like papules; a sign of disseminated cryptococcosis.
▪ Talaromycosis (Talaromyces marneffei) — umbilicated papules with central necrosis on face and trunk; endemic in north-east India, Thailand, southern China. [VERY HIGH-YIELD]
▪ Drug eruptions — morbilliform rash (nevirapine, cotrimoxazole, efavirenz, abacavir), and severe reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS).
▪ Hair changes — thinning, premature greying, straightening of curly hair.
▪ Nail changes — clubbing, longitudinal melanonychia (zidovudine), onychomycosis, yellow nails.
▪ Pigmentary changes — diffuse hyperpigmentation, mucocutaneous pigmentation.
▪ Psoriasis — new onset or severe exacerbation may indicate HIV.
▪ Visual acuity in both eyes at every visit when CD4 < 100. [IMPORTANT]
▪ Dilated fundoscopy — mandatory at CD4 < 50, or with any visual symptom.
▪ CMV retinitis — perivascular yellow-white retinal necrosis with haemorrhage ("pizza-pie", "cottage-cheese-and-ketchup" fundus); typically CD4 < 50. [FAVORITE EXAM QUESTION]
▪ HIV retinopathy — cotton-wool spots without inflammation; the commonest retinal finding; asymptomatic and non-progressive.
▪ Toxoplasma retinochoroiditis — focal necrotising retinitis with dense vitritis ("headlight in the fog").
▪ Acute retinal necrosis — VZV/HSV; peripheral confluent necrosis with rapid progression and arteritis; a surgical emergency.
▪ Ocular syphilis — panuveitis, papillitis, placoid chorioretinitis; treat as neurosyphilis.
▪ Herpes zoster ophthalmicus — V1 dermatome vesicles, Hutchinson sign (nasociliary involvement).
▪ Kaposi sarcoma of the conjunctiva or eyelid; and microvasculopathy of the conjunctiva.
▪ Tuberculosis — cough > 2 weeks, fever, night sweats, weight loss; any one symptom mandates TB evaluation in PLHIV (the 4-symptom screen). [VERY HIGH-YIELD]
▪ Pneumocystis pneumonia — subacute exertional dyspnoea, dry cough, remarkably normal auscultation despite marked hypoxaemia and exertional desaturation.
▪ Bacterial pneumonia — acute onset, focal consolidation; recurrent (≥ 2 episodes/year) is AIDS-defining.
▪ Pleural effusion — TB, empyema, Kaposi sarcoma, lymphoma; examine for stony dullness and reduced breath sounds.
▪ Fungal infection — cryptococcosis, histoplasmosis, talaromycosis, aspergillosis.
▪ Pulmonary Kaposi sarcoma — nodular infiltrates, endobronchial lesions, haemoptysis; associated with cutaneous/palatal KS.
▪ Pulmonary hypertension — loud P2, parasternal heave, raised JVP; HIV-associated PAH is an independent entity.
▪ Cardiomyopathy — displaced apex, gallop rhythm, features of heart failure.
▪ Pericardial effusion — muffled sounds, raised JVP, pulsus paradoxus; tuberculous pericarditis is the commonest cause in India. [VERY HIGH-YIELD]
▪ Myocarditis — HIV itself, CMV, toxoplasma.
▪ Infective endocarditis — especially in PWID; right-sided (tricuspid) Staphylococcus aureus endocarditis.
▪ Pulmonary hypertension and atherosclerotic disease — premature coronary and cerebrovascular disease; assess pulses, bruits and ASCVD risk.
▪ Hepatomegaly — TB, MAC, fungal infection, viral hepatitis, drug injury, fatty liver, lymphoma.
▪ Splenomegaly — TB, visceral leishmaniasis (Bihar/Jharkhand belt), lymphoma, histoplasmosis, portal hypertension.
▪ Ascites — tuberculous peritonitis, chronic liver disease, malignancy.
▪ Abdominal lymphadenopathy — palpable masses; abdominal TB and lymphoma.
▪ Chronic liver disease — spider naevi, palmar erythema, caput medusae; HBV/HCV coinfection.
▪ Abdominal mass — lymphoma, TB mass, intussusception in children.
▪ Opportunistic gastrointestinal disease — oral/oesophageal candidiasis, CMV colitis, cryptosporidiosis; check for perianal disease and fistulae.
▪ Cognitive screening — International HIV Dementia Scale (IHDS) or MoCA; assess memory, psychomotor speed and attention. [IMPORTANT]
▪ Meningeal signs — neck stiffness and Kernig sign are frequently absent in cryptococcal meningitis; a normal neck does not exclude it. [VERY HIGH-YIELD]
▪ Cranial nerves — papilloedema (raised ICP), VI nerve palsy (false localising), VII palsy, VIII involvement.
▪ Motor system — hemiparesis (toxoplasmosis, lymphoma, tuberculoma, PML, stroke), spasticity.
▪ Sensory system — glove-and-stocking loss of pain/temperature in distal symmetrical polyneuropathy.
▪ Cerebellar signs — PML, cerebellar toxoplasmosis, drug toxicity.
▪ Gait — spastic-ataxic gait of vacuolar myelopathy; sensory ataxia of neuropathy.
▪ Peripheral neuropathy — painful burning feet; commonest neurological complication; from HIV itself or from stavudine/didanosine/isoniazid.
▪ Myelopathy — vacuolar myelopathy: spastic paraparesis, sensory ataxia and sphincter disturbance, with no sensory level (unlike compressive lesions). [COMMON MCQ]
▪ Autonomic dysfunction — postural hypotension, impotence, gastroparesis, sweating abnormalities.
▪ Fundoscopy for papilloedema before lumbar puncture in any patient with focal signs or altered sensorium.
▪ Genital ulcers — differentiate painful (HSV, chancroid) from painless (primary syphilis, granuloma inguinale).
▪ HSV — recurrent grouped vesicles/ulcers; chronic ulceration > 1 month is AIDS-defining.
▪ Syphilis — chancre, condylomata lata, mucous patches; always send VDRL/RPR + treponemal test.
▪ HPV warts (condylomata acuminata) — extensive, recurrent, treatment-resistant in HIV.
▪ Vaginal discharge — candidiasis (recurrent, refractory), trichomoniasis, bacterial vaginosis.
▪ Cervical lesions — mandatory speculum examination and cervical cancer screening; HPV-related CIN progresses faster in HIV. [VERY HIGH-YIELD]
▪ Anal lesions — warts, fissures, fistulae, anal intraepithelial neoplasia, anal carcinoma.
▪ Proctitis — pain, tenesmus, discharge; gonorrhoea, chlamydia (LGV), HSV, syphilis.
▪ Testicular disease — TB epididymo-orchitis, seminoma, hypogonadism (small soft testes).
|
The Three "C"s of HIV Testing [VERY HIGH-YIELD] Consent · Confidentiality · Counselling — enshrined in Indian law under the HIV and AIDS (Prevention and Control) Act, 2017. ▪ Informed consent must be obtained; HIV testing must never be done without the person's knowledge, nor as a condition of employment, education, insurance or healthcare. ▪ Confidentiality — results may be shared only with the person, and with a healthcare provider directly involved in care. ▪ Voluntary testing — no compulsory or mandatory testing (exception: screening of donated blood, organs, tissue and semen, which is on the specimen, not the person). |
▪ Provider-initiated testing and counselling (PITC) — offered routinely to patients with TB, STIs, hepatitis, pregnancy, or any suggestive clinical condition; the person retains the right to opt out.
▪ Client-initiated (voluntary) testing — at ICTCs on request.
▪ Pre-test information — nature of the test, window period, meaning of results, confidentiality, benefit of early treatment.
▪ Post-test counselling — for both positive and negative results; risk reduction, partner testing, retesting if in the window period.
▪ Linkage to care — same-day registration at an ART centre; ideally same-day ART initiation.
▪ Partner notification — voluntary, assisted partner notification is preferred; under the 2017 Act disclosure without consent is permitted only by court order.
▪ Testing in minors — in India, a person aged 12 years or above who is sufficiently mature may give independent consent for HIV testing and to access their own records; below 12 years, consent is from the parent or guardian. [IMPORTANT]
▪ Testing during pregnancy — offered to all pregnant women at first ANC visit; retest in the third trimester in high-burden settings; test partner too.
▪ Testing after sexual assault — baseline test with consent, PEP offered irrespective, follow-up at 6 weeks, 3 and 6 months; forensic and psychosocial pathway must run in parallel.
▪ Testing after occupational exposure — baseline plus 6-week, 3-month and 6-month tests; source testing with consent.
▪ HIV self-testing — WHO-recommended; a reactive self-test is always a screening result requiring confirmation at a facility.
|
Test |
What it detects |
Main use |
|
Antibody tests (ELISA, rapid) |
Anti-HIV IgG ± IgM |
Screening and confirmation in adults |
|
Antigen-antibody (combo) tests |
p24 antigen + antibody |
Fourth-generation screening; shortens window |
|
p24 antigen assay |
Capsid protein |
Early/acute infection |
|
HIV-1 RNA (viral load) |
Plasma viral RNA |
Acute infection, monitoring, infant diagnosis |
|
HIV-1 DNA PCR |
Proviral DNA in cells |
Infant diagnosis — unaffected by maternal antibody |
|
HIV-2 specific tests |
HIV-2 antibody / RNA / DNA |
Suspected HIV-2 or dual infection |
|
Rapid / point-of-care tests |
Antibody ± antigen |
ICTC, outreach, labour room; result in 15–30 minutes |
|
Dried blood spots (DBS) |
Antibody / RNA / DNA |
Infant diagnosis and viral load in remote settings |
|
Western blot / line immunoassay |
Antibodies to individual proteins |
Historic confirmatory test; no longer recommended by WHO/NACO |
|
Generation |
Antigen used / detects |
Window period |
|
First generation |
Viral lysate; detects IgG only |
~6–12 weeks |
|
Second generation |
Recombinant/synthetic peptide antigens; IgG |
~3–4 weeks |
|
Third generation |
Sandwich format; detects IgM and IgG |
~20–25 days |
|
Fourth generation |
p24 antigen + IgM/IgG antibody |
~15–20 days [VERY HIGH-YIELD] |
|
HIV RNA (NAT) |
Viral nucleic acid |
~10 days — the shortest window |
▪ Window period = the interval between infection and the earliest detection by a given assay; a person is infectious throughout.
▪ Sensitivity of modern assays > 99.5% — very few false negatives outside the window period.
▪ Specificity > 99% but not 100% — false-positive screening results occur with pregnancy, autoimmune disease, multiple transfusions, recent vaccination, malaria, other infections and multiparity; hence the requirement for a testing strategy, never a single test. [IMPORTANT]
▪ Limitations: window period, HIV-2 and group O may be missed by some assays, infants have maternal antibody, and a person on PrEP/PEP or very early ART may have blunted serology.
|
NACO Testing Strategies (WHO-aligned) [VERY HIGH-YIELD] ▪ Strategy I (one test): blood, organ, tissue and semen donor screening. Any reactive unit is discarded. ▪ Strategy II (up to two tests): surveillance (unlinked anonymous testing). ▪ Strategy IIA: diagnosis in a symptomatic individual — two sequential reactive tests confirm. ▪ Strategy III (three tests): diagnosis in an asymptomatic individual — three sequential reactive tests (A1, A2, A3) confirm the diagnosis. Golden rule: the three tests must use different antigen preparations or different test principles to avoid repeating the same false positive. |
|
|
NACO Three-Test Algorithm for an Asymptomatic Adult Blood sample → Test A1 (most sensitive assay) ↓ If A1 non-reactive → report HIV NEGATIVE (advise retest at 6 and 12 weeks if recent exposure) If A1 reactive → proceed to Test A2 (different antigen/principle) ↓ A1+ / A2+ → proceed to Test A3 (third different antigen/principle) A1+ / A2− → repeat both; if still discordant → report INDETERMINATE, retest after 2–4 weeks ↓ A1+ / A2+ / A3+ → report HIV POSITIVE — link to ART centre the same day A1+ / A2+ / A3− → report INDETERMINATE — repeat after 14–28 days; consider HIV RNA |
|
▪ Blood-donor screening: every donated unit is screened for HIV, HBsAg, anti-HCV, syphilis and malaria; reactive units are discarded and the donor referred for confirmatory testing and counselling.
▪ Discordant results — reactive on one assay, non-reactive on another; repeat on a fresh sample and use a fourth-generation assay or NAT.
▪ Inconclusive / indeterminate results — repeat after 2–4 weeks; consider acute infection (do HIV RNA), HIV-2, or a non-specific reaction.
▪ Repeat testing after a negative result is essential if exposure occurred within the window period — retest at 6 weeks and 3 months (and 6 months after occupational exposure or if on PEP).
▪ The classic pattern is HIV RNA positive with antibody negative ("seronegative window infection"). [VERY HIGH-YIELD]
▪ p24 antigen detection — present between roughly day 14 and the appearance of antibody.
▪ Fourth-generation testing with a reactive antigen but non-reactive antibody differentiation strongly suggests acute infection.
▪ Repeat serology at 2–4 weeks documents seroconversion and confirms the diagnosis.
▪ False-positive RNA considerations: a low-level positive (< 5000 copies/mL) with negative serology may be a false positive — always repeat before labelling the person infected. Genuine acute infection almost always has a very high viral load. [IMPORTANT]
|
Why Antibody Tests Fail in Infants [FAVORITE EXAM QUESTION] Maternal IgG crosses the placenta and persists in the infant for up to 18 months. An antibody test in an infant therefore reflects maternal, not infant, infection. → Diagnosis under 18 months requires virological testing: HIV DNA PCR or HIV RNA PCR (usually on a dried blood spot). |
||
|
Age / situation |
Test |
|
|
Birth to 18 months |
HIV DNA PCR (or RNA PCR) on DBS |
|
|
At birth (high-risk infants) |
Birth PCR at 0–2 days, then per schedule |
|
|
6 weeks (all HIV-exposed infants) |
First routine DNA PCR — the standard NACO time point |
|
|
6 months and 12 months |
Repeat PCR if still breastfeeding |
|
|
6 weeks after complete cessation of breastfeeding |
Repeat PCR — breastfeeding is a continuing exposure [VERY HIGH-YIELD] |
|
|
18 months |
Final confirmation by antibody test (three-test strategy) |
|
|
Any age with symptoms |
Immediate virological test — do not wait for the schedule |
|
▪ Two positive virological tests on separate specimens confirm infant HIV infection; ART must be started immediately in any infant with a single positive test while awaiting confirmation. [IMPORTANT]
▪ All HIV-exposed infants receive ARV prophylaxis and cotrimoxazole prophylaxis from 6 weeks until infection is definitively excluded.
▪ HIV-2 — suspect with positive screening but persistently low/undetectable HIV-1 RNA, West African origin, or an indeterminate differentiation assay; use HIV-2 specific serology and NAT.
▪ Dual HIV-1/HIV-2 infection — requires discriminatory serology; treat with a regimen active against both.
▪ Advanced immunosuppression — very rare loss of antibody (seroreversion) in end-stage disease; use p24 antigen or RNA.
▪ Recent PEP or PrEP — may delay or blunt seroconversion, prolonging the window; extend follow-up testing to 3–6 months and use RNA if suspicion is high. [IMPORTANT]
▪ ART started during acute infection — may abort the antibody response, giving persistently negative or indeterminate serology; diagnosis rests on the documented pre-treatment RNA/antigen result.
▪ Indeterminate serology — causes include early seroconversion, HIV-2, autoimmune disease, pregnancy, multiple transfusions and cross-reactivity; repeat in 2–4 weeks with a NAT.
▪ Passive antibody transfer — maternal antibody in infants; also after immunoglobulin, monoclonal antibody therapy or participation in a vaccine trial (vaccine-induced seropositivity, "VISP").
▪ Symptoms and signs — full systemic review with emphasis on fever, weight loss, cough, diarrhoea, headache, visual and neurological symptoms.
▪ WHO clinical stage assignment (1–4) at entry to care. [IMPORTANT]
▪ Active screening for opportunistic infections — TB four-symptom screen, oral/oesophageal candidiasis, cryptococcal disease, CMV.
▪ Pregnancy status and intention in all women of reproductive age.
▪ Comorbidities — diabetes, hypertension, cardiovascular disease, chronic kidney/liver disease, epilepsy, thyroid disease.
▪ Mental health — depression, anxiety, suicidal ideation (PHQ-9/GAD-7 where feasible).
▪ Substance use — alcohol, tobacco, injecting and non-injecting drugs.
▪ Adherence readiness — understanding of lifelong therapy, daily routine, pill-taking plan, treatment supporter.
▪ Social support and disclosure status — family awareness, peer support, food security, cost of transport.
▪ Confirmed HIV test result documented (three-test strategy or as per algorithm).
▪ CD4 count and CD4 percentage — determines advanced disease, OI prophylaxis and prognosis. CD4 % is preferred in children < 5 years.
▪ Plasma viral load — baseline value predicts time to suppression and, later, defines failure.
▪ Complete blood count with peripheral smear — anaemia, cytopenias, malaria/leishmania in relevant regions.
▪ Liver function tests — before nevirapine, and to detect coinfection and drug injury.
▪ Renal function — serum creatinine with eGFR; electrolytes; urinalysis and quantified proteinuria (essential before tenofovir). [VERY HIGH-YIELD]
▪ Blood glucose and HbA1c; fasting lipid profile — baseline metabolic risk.
▪ Pregnancy test in women of reproductive age.
▪ HBsAg, anti-HBc and anti-HBs — determines HBV-active ART and vaccination need. [IMPORTANT]
▪ Anti-HCV — with HCV RNA if reactive; mandatory in PWID.
▪ Syphilis — VDRL/RPR plus a treponemal test.
▪ Gonorrhoea and chlamydia testing — NAAT of urine/genital/rectal/pharyngeal sites in those at risk.
▪ Tuberculosis symptom screen at every visit (current cough, fever, weight loss, night sweats) plus chest radiograph and sputum molecular test (CBNAAT / Truenat) if screen-positive. [VERY HIGH-YIELD]
▪ Serum cryptococcal antigen (CrAg) — screen all patients with CD4 < 200 cells/µL (NACO/WHO) to detect asymptomatic cryptococcal antigenaemia.
▪ Toxoplasma IgG — identifies those at risk of reactivation and needing prophylaxis.
▪ CMV evaluation — dilated fundoscopy if CD4 < 50; CMV serology/PCR where indicated.
▪ Cervical cancer screening — Pap smear/VIA/HPV testing at diagnosis and annually or as per national guidance for women with HIV.
▪ Anal cancer assessment — digital anorectal examination ± anal cytology in MSM, transgender women and women with cervical dysplasia.
▪ HLA-B*57:01 — must be negative before prescribing abacavir (predicts hypersensitivity); not routine in India where abacavir use is limited. [VERY HIGH-YIELD]
▪ G6PD testing — before dapsone or primaquine.
▪ Baseline resistance genotype — recommended where transmitted resistance exceeds 10%, and for all infants, pregnant women and those failing therapy.
▪ Coreceptor tropism testing — only if maraviroc is contemplated.
▪ Bone-health assessment — fracture risk (FRAX), vitamin D, DEXA in those over 50 or with risk factors on tenofovir.
▪ Cardiovascular risk assessment — ASCVD/Framingham score, blood pressure, smoking status, lipids.
▪ Viral load is the gold standard for monitoring ART. [VERY HIGH-YIELD]
▪ Baseline viral load before initiation; NACO schedule: viral load at 6 months, 12 months, and annually thereafter once suppressed.
▪ Expected decline: ≥ 1 log₁₀ fall by week 4; undetectable by 12–24 weeks.
▪ Virological suppression: < 50 copies/mL (programme threshold < 1000 copies/mL).
▪ Viral blip — isolated 50–200 copies/mL with spontaneous return to undetectable; not failure, no action but reinforce adherence.
▪ Low-level viraemia — persistent 50–1000 copies/mL; associated with a higher risk of subsequent failure; intensify adherence and repeat.
▪ Persistent viraemia / virological failure — > 1000 copies/mL on two occasions ≥ 3 months apart despite adherence support. [FAVORITE EXAM QUESTION]
▪ Repeat testing after enhanced adherence counselling (EAC) — three sessions of EAC over 3 months, then repeat viral load before declaring failure.
|
NACO Approach to a High Viral Load [VERY HIGH-YIELD] Routine viral load > 1000 copies/mL ↓ Enhanced adherence counselling — 3 monthly sessions; check drug interactions, dosing errors, malabsorption, drug stock-outs ↓ Repeat viral load after 3 months ↓ < 1000 copies/mL → adherence problem resolved; continue same regimen and monitor > 1000 copies/mL → confirmed virological failure ↓ Refer to Centre of Excellence / State AIDS Clinical Expert Panel (SACEP) → resistance testing where available → switch regimen |
▪ CD4 count at baseline and 6-monthly until stable and > 350 cells/µL with viral suppression.
▪ CD4 percentage — the preferred parameter in children under 5 years, where absolute counts vary with age.
▪ CD4 recovery — typically +50–100 cells/µL in the first 3 months (redistribution), then ~50–100 cells/µL per year to a plateau.
▪ Discordant response — virological suppression without adequate CD4 rise (immunological non-response); associated with low nadir CD4, older age, HCV coinfection, and lymphoid fibrosis.
▪ Poor immunological recovery — predicts higher risk of both AIDS and non-AIDS events; there is no proven intervention other than continued ART and comorbidity control. [IMPORTANT]
▪ Role in OI prophylaxis — CD4 thresholds determine when to start and when to stop cotrimoxazole, and CrAg screening.
▪ Reduced CD4 monitoring is recommended in stable patients (suppressed viral load, CD4 > 350) — CD4 may then be checked only when clinically indicated.
▪ Weight and BMI at every visit — unexplained weight loss is an early sign of TB, failure or malignancy.
▪ New symptoms — TB four-symptom screen, headache, visual change, diarrhoea, dyspnoea, skin lesions.
▪ Opportunistic infections — new or recurrent events indicate clinical failure or IRIS.
▪ IRIS — anticipate in the first 4–12 weeks after ART, especially with low CD4 and treated TB or cryptococcal disease.
▪ Drug adverse effects — targeted enquiry at each visit.
▪ Adherence — pill count, refill record, self-report; the strongest predictor of outcome.
▪ Pregnancy — plan or confirm; adjust regimen and add PPTCT care.
▪ Mental health — depression and substance use screening at least annually.
▪ Cardiovascular and metabolic risk — BP, lipids, glucose, smoking; annual review.
|
Toxicity |
Drug(s) |
Monitoring |
|
Renal toxicity |
Tenofovir disoproxil fumarate (TDF) |
Creatinine/eGFR, urine protein, phosphate — at baseline, 3, 6 months, then yearly [VERY HIGH-YIELD] |
|
Hepatotoxicity |
Nevirapine, efavirenz, PIs, TB drugs |
ALT at baseline and with symptoms; NVP requires close monitoring in the first 12 weeks |
|
Bone toxicity |
TDF |
Fracture history, vitamin D, DEXA if risk factors |
|
Dyslipidaemia |
PIs, efavirenz |
Fasting lipids yearly |
|
Hyperglycaemia / insulin resistance |
PIs, dolutegravir (weight gain) |
Fasting glucose, HbA1c yearly |
|
Anaemia |
Zidovudine (AZT) |
Hb at baseline, 1, 3, 6 months |
|
Neutropenia |
Zidovudine, cotrimoxazole, ganciclovir |
CBC as indicated |
|
Pancreatitis |
Didanosine, stavudine (largely withdrawn) |
Serum amylase/lipase if abdominal pain |
|
Lactic acidosis |
Stavudine, didanosine, zidovudine |
Lactate only if symptomatic — nausea, weight loss, dyspnoea, hepatomegaly |
|
Hypersensitivity |
Abacavir, nevirapine, cotrimoxazole |
HLA-B*57:01 before abacavir; clinical vigilance for rash and fever |
|
QT prolongation |
Some PIs, bedaquiline, fluoroquinolones, azoles |
ECG when combining QT-prolonging drugs |
|
Neuropsychiatric effects |
Efavirenz, dolutegravir, rilpivirine |
Enquire about insomnia, vivid dreams, mood change, suicidality |
|
Type of failure |
Definition |
|
Clinical failure |
New or recurrent WHO stage 4 condition (or certain stage 3) after ≥ 6 months of ART, excluding IRIS |
|
Immunological failure |
CD4 falls to or below the pre-treatment baseline, or persists < 250 cells/µL after clinical failure |
|
Virological failure |
Viral load > 1000 copies/mL on two consecutive measurements ≥ 3 months apart with adherence support — the definitive criterion [VERY HIGH-YIELD] |
|
Adherence failure |
The commonest underlying reason — missed doses, interruptions, stock-outs, migration |
▪ Before declaring drug resistance, exclude:
– Poor adherence — the commonest cause by far.
– Drug–drug interactions — rifampicin, anticonvulsants, antacids, calcium/iron, PPIs, herbal products.
– Malabsorption — chronic diarrhoea, vomiting, gastrointestinal opportunistic disease.
– Incorrect dosage or administration — food requirements, paediatric dosing not adjusted for weight, split doses.
– Drug quality or supply interruption — stock-outs, storage in heat.
▪ Only when these are excluded should drug resistance be assumed and a regimen switch made — preferably guided by a genotype and an expert panel. [IMPORTANT]
▪ Management approach: confirm with repeat VL after EAC → assess resistance → switch to a regimen with at least two (preferably three) fully active drugs → never add a single drug to a failing regimen ("functional monotherapy").
▪ Based purely on clinical events, requiring no laboratory tests — ideal for resource-limited settings; used by NACO. [VERY HIGH-YIELD]
▪ Asymptomatic infection.
▪ Persistent generalised lymphadenopathy (PGL) — nodes > 1 cm at ≥ 2 extra-inguinal sites for > 3 months.
▪ Unexplained moderate weight loss (< 10%) of body weight.
▪ Recurrent upper respiratory tract infections — sinusitis, tonsillitis, otitis media, pharyngitis.
▪ Herpes zoster.
▪ Angular cheilitis; recurrent oral ulceration.
▪ Papular pruritic eruption; seborrhoeic dermatitis; fungal nail infections.
▪ Unexplained severe weight loss (> 10%) of body weight.
▪ Unexplained chronic diarrhoea for > 1 month.
▪ Unexplained persistent fever > 1 month (intermittent or constant).
▪ Persistent oral candidiasis; oral hairy leukoplakia.
▪ Pulmonary tuberculosis.
▪ Severe bacterial infections — pneumonia, empyema, pyomyositis, bone/joint infection, meningitis, bacteraemia.
▪ Acute necrotising ulcerative stomatitis, gingivitis or periodontitis.
▪ Unexplained anaemia (< 8 g/dL), neutropenia (< 0.5 × 10⁹/L) or chronic thrombocytopenia (< 50 × 10⁹/L).
▪ HIV wasting syndrome.
▪ Pneumocystis jirovecii pneumonia.
▪ Recurrent severe bacterial pneumonia.
▪ Chronic herpes simplex (orolabial, genital or anorectal for > 1 month, or visceral).
▪ Oesophageal candidiasis (or of trachea, bronchi or lungs).
▪ Extrapulmonary tuberculosis.
▪ Kaposi sarcoma.
▪ CMV disease (retinitis or of other organs except liver, spleen, lymph nodes).
▪ CNS toxoplasmosis.
▪ HIV encephalopathy.
▪ Extrapulmonary cryptococcosis including meningitis.
▪ Disseminated non-tuberculous mycobacterial infection.
▪ Progressive multifocal leukoencephalopathy (PML).
▪ Chronic cryptosporidiosis or isosporiasis (with diarrhoea > 1 month).
▪ Disseminated mycosis — histoplasmosis, coccidioidomycosis, talaromycosis.
▪ Recurrent non-typhoidal Salmonella bacteraemia.
▪ Lymphoma — cerebral or B-cell non-Hodgkin.
▪ Invasive cervical carcinoma.
▪ Atypical disseminated leishmaniasis.
▪ Symptomatic HIV-associated nephropathy or cardiomyopathy.
|
Staging Notes ▪ Adults and adolescents use the staging above; children have a paediatric version with additional items (unexplained persistent hepatosplenomegaly, lymphoid interstitial pneumonitis, chronic HIV-associated lung disease, severe recurrent bacterial infection, and severe acute malnutrition unresponsive to therapy). ▪ Limitations after ART initiation: WHO staging reflects the worst-ever stage; it does not improve with immune recovery, so it cannot be used to judge treatment response. Use viral load for that. [IMPORTANT] |
|
CDC stage |
Criteria (adults and adolescents ≥ 6 years) |
|
Stage 0 |
A negative or indeterminate HIV test within 180 days before the first confirmed positive test — i.e. early/recent infection; supersedes all other stages for 180 days |
|
Stage 1 |
CD4 ≥ 500 cells/µL (or CD4 ≥ 26%) and no AIDS-defining condition |
|
Stage 2 |
CD4 200–499 cells/µL (or CD4 14–25%) and no AIDS-defining condition |
|
Stage 3 (AIDS) |
CD4 < 200 cells/µL (or CD4 < 14%) or the presence of any stage-3-defining opportunistic illness |
|
Unknown stage |
No CD4 information and no information on AIDS-defining conditions |
▪ Stage-3-defining illnesses are the classic AIDS-defining conditions listed in section 13.4.
▪ CDC staging is chiefly a surveillance tool; WHO staging is the clinical management tool used in India. [COMMON MCQ]
|
CD4 count |
Immune status |
Characteristic infections at this level |
|
|
> 500 cells/µL |
Normal / minimal deficiency |
Acute retroviral syndrome, PGL; TB and bacterial pneumonia can occur at any CD4 [IMPORTANT] |
|
|
200–499 cells/µL |
Mild-to-moderate deficiency |
TB, herpes zoster, oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, bacterial pneumonia, seborrhoeic dermatitis |
|
|
< 200 cells/µL |
Severe deficiency (AIDS) |
Pneumocystis pneumonia, oesophageal candidiasis, disseminated/miliary TB, cryptococcosis |
|
|
< 100 cells/µL |
Advanced |
Cerebral toxoplasmosis, cryptococcal meningitis, chronic cryptosporidiosis, HIV wasting, PML, disseminated histoplasmosis/talaromycosis |
|
|
< 50 cells/µL |
Profound |
CMV retinitis and colitis, disseminated MAC, primary CNS lymphoma, PML [VERY HIGH-YIELD] |
|
|
CD4 Thresholds — Must Memorise [FAVORITE EXAM QUESTION] < 200 → PCP · < 100 → Toxoplasmosis, Cryptococcus · < 50 → CMV, MAC Mnemonic: "200 Pneumocystis, 100 Toxo/Crypto, 50 CMV/MAC" Tuberculosis is the exception — it occurs at any CD4 count and is the commonest OI in India. |
|||
▪ Definition in adults, adolescents and children ≥ 5 years: CD4 < 200 cells/µL or WHO stage 3 or 4.
▪ Definition in children < 5 years: all children with HIV are considered to have advanced disease, except those already stable on ART.
▪ Rapid assessment: immediate TB symptom screen and urine LF-LAM, serum CrAg if CD4 < 200, and evaluation for other OIs, before or alongside ART initiation.
|
WHO/NACO Package of Care for Advanced HIV Disease [VERY HIGH-YIELD] 1. Screening for tuberculosis — four-symptom screen + urine LF-LAM (recommended when CD4 < 200 or seriously ill) + CBNAAT/Truenat + chest X-ray. 2. Cryptococcal antigen (CrAg) screening — serum/plasma CrAg for all with CD4 < 200; if positive, perform lumbar puncture to exclude meningitis; if meningitis excluded, give pre-emptive fluconazole. 3. Cotrimoxazole prophylaxis — start immediately for PCP, toxoplasmosis, bacterial infection and malaria. 4. TB preventive therapy once active TB is excluded. 5. Rapid ART initiation — start within 7 days once OIs are addressed, but DELAY ART in cryptococcal meningitis (4–6 weeks) and in TB meningitis (~4–8 weeks) because of the risk of fatal IRIS. [FAVORITE EXAM QUESTION] 6. Intensified adherence support and follow-up — the first 6 months carry the highest mortality. |
▪ Bacterial: recurrent bacterial pneumonia (≥ 2 in 12 months); recurrent non-typhoidal Salmonella septicaemia; Mycobacterium tuberculosis (pulmonary or extrapulmonary); disseminated Mycobacterium avium complex or other non-tuberculous mycobacteria.
▪ Fungal: Pneumocystis jirovecii pneumonia; oesophageal, tracheal, bronchial or pulmonary candidiasis; extrapulmonary cryptococcosis; disseminated histoplasmosis; disseminated coccidioidomycosis; disseminated talaromycosis (penicilliosis).
▪ Protozoal: cerebral toxoplasmosis; chronic cryptosporidiosis (> 1 month); chronic cystoisosporiasis (isosporiasis, > 1 month); atypical disseminated leishmaniasis.
▪ Viral: CMV disease other than liver, spleen or nodes (including CMV retinitis); chronic herpes simplex ulceration > 1 month or visceral HSV; progressive multifocal leukoencephalopathy (JC virus).
▪ Kaposi sarcoma.
▪ Non-Hodgkin lymphoma — Burkitt, immunoblastic/diffuse large B-cell.
▪ Primary CNS lymphoma.
▪ Invasive cervical carcinoma. [VERY HIGH-YIELD]
▪ HIV wasting syndrome — involuntary loss of > 10% body weight plus chronic diarrhoea or chronic weakness and documented fever for ≥ 30 days, with no other explanation.
▪ HIV encephalopathy — disabling cognitive/motor dysfunction interfering with daily activity, progressing over weeks to months, without another cause.
▪ HIV-associated nephropathy and cardiomyopathy (WHO stage 4 when symptomatic).
▪ Lymphoid interstitial pneumonitis in children.
|
How to Approach Any Presenting Problem in HIV [VERY HIGH-YIELD] Four questions answer most clinical problems in HIV: 1. What is the CD4 count? — it defines the differential diagnosis. 2. Is the patient on ART, and for how long? — recent initiation raises IRIS; long duration raises failure and drug toxicity. 3. Is the patient on prophylaxis? — cotrimoxazole essentially excludes PCP and toxoplasmosis if truly adherent. 4. Could this be tuberculosis? — in India, until proved otherwise, it usually is. |
▪ Acute fever (< 2 weeks) — bacterial infection, malaria, dengue, enteric fever, acute HIV, drug reaction.
▪ Chronic fever (> 2 weeks) — tuberculosis, disseminated fungal infection, MAC, lymphoma, visceral leishmaniasis.
▪ Fever with localising signs — direct evaluation to the affected system.
▪ Fever without localising signs (PUO in HIV) — in India, disseminated tuberculosis is the commonest cause by a wide margin. [VERY HIGH-YIELD]
|
CD4 count |
Likely causes of fever |
|
Any CD4 |
Tuberculosis, bacterial infection, malaria, dengue, enteric fever, drug fever, lymphoma |
|
< 200 |
PCP, disseminated TB, cryptococcosis, histoplasmosis, talaromycosis (north-east India) |
|
< 100 |
Toxoplasmosis, visceral leishmaniasis, disseminated fungal disease |
|
< 50 |
Disseminated MAC, CMV disease, lymphoma [FAVORITE EXAM QUESTION] |
▪ Tuberculosis — pulmonary, extrapulmonary, disseminated; the commonest cause of fever and of death.
▪ Bacterial infection — pneumonia, urinary tract infection, bacteraemia (pneumococcus, Salmonella, Staphylococcus).
▪ Cryptococcosis — fever with headache; always send serum CrAg.
▪ Histoplasmosis — fever, weight loss, hepatosplenomegaly, pancytopenia, mucosal ulcers, adrenal involvement.
▪ Talaromycosis — fever, umbilicated skin papules, anaemia, hepatosplenomegaly; endemic in Manipur and north-east India.
▪ MAC — fever, night sweats, weight loss, diarrhoea, anaemia, raised alkaline phosphatase at CD4 < 50.
▪ CMV — fever with retinitis, colitis or oesophagitis.
▪ Malignancy — lymphoma, Castleman disease (fever with lymphadenopathy and cytopenias).
▪ Drug fever — cotrimoxazole, abacavir, nevirapine, efavirenz; look for rash and eosinophilia.
▪ IRIS — fever within 4–12 weeks of starting ART with paradoxical worsening of a treated OI.
▪ CBC with differential and peripheral smear; ESR/CRP; blood cultures (bacterial × 2 sets and mycobacterial); LFT, RFT.
▪ Sputum CBNAAT/Truenat and culture; urine LF-LAM if CD4 < 200 or seriously ill.
▪ Chest radiograph; ultrasound abdomen (nodes, splenic microabscesses, ascites); CT chest/abdomen if available.
▪ Serum cryptococcal antigen; fungal blood cultures; Histoplasma/Talaromyces antigen where available.
▪ Malaria smear/RDT, dengue NS1/IgM, Widal/blood culture as regionally appropriate; rK39 for visceral leishmaniasis in endemic belts.
▪ Bone-marrow aspirate and biopsy — high yield for disseminated TB, MAC, fungi, leishmania and lymphoma in prolonged undiagnosed fever. [IMPORTANT]
▪ Lymph-node FNAC/biopsy; CD4 count and viral load; fundoscopy if CD4 < 50.
|
Management Algorithm — Fever in HIV Fever in a person living with HIV ↓ Assess haemodynamic stability — if septic, resuscitate and give broad-spectrum antibiotics immediately ↓ Check CD4 count, ART status and prophylaxis history ↓ Screen for TB in every patient — symptoms, sputum CBNAAT, chest X-ray, urine LF-LAM if CD4 < 200 ↓ Localising features present → direct investigation to that system No localising features → blood/mycobacterial cultures, serum CrAg, USG abdomen, malaria/dengue workup ↓ Still undiagnosed after 1 week → bone-marrow aspirate + biopsy ± CT-guided node biopsy ↓ Empirical anti-tuberculosis therapy may be justified in a deteriorating patient with high clinical suspicion in India — document the rationale ↓ Treat the cause; start/continue ART; add cotrimoxazole prophylaxis if CD4 < 200 |
▪ Reduced intake — oral/oesophageal candidiasis, painful ulcers, anorexia, depression, poverty and food insecurity.
▪ Chronic diarrhoea and malabsorption — cryptosporidiosis, microsporidiosis, MAC, HIV enteropathy.
▪ Tuberculosis and other disseminated infections — the commonest cause of weight loss in Indian PLHIV. [VERY HIGH-YIELD]
▪ Malignancy — lymphoma, Kaposi sarcoma, cervical or anal carcinoma.
▪ Endocrine disease — adrenal insufficiency (CMV adrenalitis, TB adrenals), hyperthyroidism, hypogonadism, diabetes.
▪ Depression and substance use.
▪ HIV wasting syndrome — > 10% involuntary weight loss with chronic diarrhoea or fever/weakness for ≥ 30 days, no other cause; an AIDS-defining condition.
▪ Nutritional assessment: weight trend, BMI, MUAC, dietary recall, serum albumin, haemoglobin; food-security enquiry.
▪ Management: treat the underlying cause (usually TB), start effective ART, high-protein high-calorie diet, micronutrients, treat oral/oesophageal disease, appetite support, link to nutrition and social-protection schemes.
▪ Persistent generalised lymphadenopathy (PGL) — nodes > 1 cm at ≥ 2 extra-inguinal sites for > 3 months, symmetrical, non-tender, mobile, no other cause; benign and needs no biopsy. [IMPORTANT]
▪ Tuberculosis — asymmetrical, matted, tender nodes, often with fever and weight loss; may suppurate or form sinuses; commonest cause of significant lymphadenopathy in India.
▪ Lymphoma — rapidly enlarging, firm, painless, often with B symptoms and raised LDH.
▪ Multicentric Castleman disease — HHV-8 driven; relapsing fever, lymphadenopathy, splenomegaly, cytopenias, very high CRP.
▪ Syphilis — secondary syphilis with rash and generalised lymphadenopathy.
▪ Fungal infection — histoplasmosis, talaromycosis, cryptococcosis.
▪ Others: Kaposi sarcoma, MAC, toxoplasmosis, CMV, drug reaction (DRESS).
|
Red Flags Mandating Node Sampling ▪ Asymmetrical, matted, tender or rapidly enlarging nodes · node > 2 cm · sinus or fluctuation ▪ Fever, night sweats, weight loss · hepatosplenomegaly · cytopenias · raised LDH FNAC with CBNAAT/Xpert on the aspirate is the first-line investigation in India; excision biopsy is required if FNAC is non-diagnostic or lymphoma is suspected. [VERY HIGH-YIELD] |
|
Cause |
Typical CD4 |
Clues |
|
Bacterial pneumonia |
Any |
Acute onset, purulent sputum, focal consolidation, high WBC |
|
Tuberculosis |
Any |
Subacute cough > 2 weeks, fever, weight loss; atypical CXR at low CD4 |
|
Pneumocystis pneumonia |
< 200 |
Subacute dry cough, exertional desaturation, normal chest signs, raised LDH |
|
Cryptococcosis |
< 100 |
Cough with headache; often disseminated; positive serum CrAg |
|
Histoplasmosis / talaromycosis |
< 100 |
Fever, hepatosplenomegaly, skin lesions, pancytopenia |
|
Nocardiosis |
< 100 |
Cavitating upper-lobe disease, brain abscess; modified acid-fast branching filaments |
|
CMV pneumonitis |
< 50 |
Diffuse interstitial infiltrates; diagnosis needs biopsy (CMV in BAL alone is not sufficient) |
|
Kaposi sarcoma |
< 200 |
Nodular infiltrates, pleural effusion, haemoptysis, endobronchial lesions with skin/palatal KS |
|
Lymphoma |
< 200 |
Mass lesions, effusion, B symptoms |
|
COPD / bronchiectasis |
Any |
Smoking, recurrent infections, chronic sputum |
|
Pulmonary hypertension |
Any |
Progressive dyspnoea, loud P2, raised JVP |
▪ Upper-lobe cavitation — classic TB (seen at higher CD4 when immunity is preserved).
▪ Miliary or lower-zone infiltrate with mediastinal nodes and normal or atypical film — TB at low CD4; up to 20% of HIV-TB have a normal chest X-ray. [VERY HIGH-YIELD]
▪ Bilateral perihilar/diffuse interstitial "ground-glass" infiltrates sparing the apices — Pneumocystis pneumonia; may show pneumatoceles and pneumothorax.
▪ Lobar consolidation — bacterial pneumonia.
▪ Nodular infiltrates along bronchovascular bundles with pleural effusion — pulmonary Kaposi sarcoma.
▪ Pleural effusion — TB (commonest), empyema, KS, lymphoma.
▪ Oxygen assessment — resting SpO₂ and exertional desaturation testing (a fall ≥ 3–5% strongly suggests PCP); ABG for A-a gradient in severe disease. [IMPORTANT]
▪ Sputum for CBNAAT/Truenat, AFB smear, culture, Gram stain and bacterial culture; blood cultures.
▪ Chest radiograph; HRCT chest when the film is normal but suspicion persists.
▪ Serum LDH — markedly raised in PCP (non-specific); serum β-D-glucan where available.
▪ Induced sputum or bronchoscopy with bronchoalveolar lavage (BAL) — for PCP (immunofluorescence, Grocott/Giemsa stain, PCR), fungi, mycobacteria, KS.
▪ Transbronchial biopsy — for CMV pneumonitis, lymphoma, KS confirmation.
▪ Pleural fluid analysis with ADA and CBNAAT if effusion present.
|
Management Algorithm — Respiratory Symptoms in HIV Cough and/or dyspnoea in a PLHIV ↓ Assess severity — SpO₂ at rest and on exertion, respiratory rate, haemodynamics ↓ Chest radiograph + sputum CBNAAT in every patient (± urine LF-LAM if CD4 < 200) ↓ Acute + focal consolidation → treat as bacterial pneumonia (amoxicillin-clavulanate + macrolide or ceftriaxone + azithromycin) Subacute + cavitation / miliary / nodes → anti-tuberculosis therapy per NTEP Subacute + diffuse interstitial + hypoxia + CD4 < 200 → treat empirically for PCP: high-dose cotrimoxazole ± steroids ↓ No response in 48–72 hours → bronchoscopy with BAL ± biopsy; reconsider fungal, CMV, KS, lymphoma ↓ Start ART (after PCP treatment begun — usually within 2 weeks); ensure cotrimoxazole prophylaxis |
|
|
Steroids in PCP [VERY HIGH-YIELD] Adjunctive corticosteroids are indicated when PaO₂ < 70 mmHg on room air or A-a gradient > 35 mmHg. Prednisolone 40 mg twice daily × 5 days → 40 mg daily × 5 days → 20 mg daily × 11 days. Steroids must be given within 72 hours of starting cotrimoxazole — they reduce mortality by preventing the inflammatory deterioration caused by organism lysis. |
|
|
Pathogen group |
Organisms and features |
|
Bacterial |
Salmonella (non-typhoidal, recurrent bacteraemia), Shigella, Campylobacter, Clostridioides difficile |
|
Mycobacterial |
MAC (CD4 < 50, fever, anaemia, raised ALP), intestinal tuberculosis (ileocaecal) |
|
Cryptosporidium |
Profuse watery, non-bloody, high-volume diarrhoea; may cause sclerosing cholangitis; modified acid-fast (Kinyoun) oocysts 4–6 µm [VERY HIGH-YIELD] |
|
Cystoisospora belli |
Watery diarrhoea with eosinophilia; large oval acid-fast oocysts 20–30 µm; responds to cotrimoxazole |
|
Cyclospora cayetanensis |
Watery diarrhoea; acid-fast oocysts 8–10 µm; autofluorescent under UV |
|
Microsporidia |
Enterocytozoon bieneusi, Encephalitozoon intestinalis; chronic watery diarrhoea; modified trichrome / Calcofluor stain |
|
Giardia lamblia |
Malabsorption, foul-smelling stools, bloating |
|
Entamoeba histolytica |
Bloody diarrhoea, colitis, liver abscess |
|
CMV colitis |
CD4 < 50; bloody diarrhoea, abdominal pain, fever; ulcers on colonoscopy; owl-eye inclusions on biopsy |
|
HIV enteropathy |
Diagnosis of exclusion; villous atrophy and malabsorption from HIV itself; improves with ART |
|
Drug-induced |
Protease inhibitors (especially lopinavir/ritonavir), didanosine, antibiotics |
|
Pancreatic disease |
Chronic pancreatitis from didanosine/stavudine → steatorrhoea |
|
Lymphoma / KS |
Bowel infiltration causing diarrhoea, bleeding or obstruction |
▪ Stool examination — routine microscopy, modified acid-fast (Kinyoun) stain for Cryptosporidium, Cystoisospora and Cyclospora; modified trichrome or Calcofluor for microsporidia; stool culture; C. difficile toxin.
▪ Stool for occult blood; three separate specimens improve yield.
▪ Blood cultures including mycobacterial (MAC) blood culture if CD4 < 50 and febrile.
▪ Endoscopy with biopsy — upper GI and colonoscopy when stool studies are negative; essential to diagnose CMV colitis, MAC, lymphoma and to confirm microsporidia.
▪ Serum electrolytes, albumin, CD4 count.
|
Management Algorithm — Chronic Diarrhoea in HIV Diarrhoea > 4 weeks in a PLHIV ↓ Rehydrate and correct electrolytes; stop culprit drugs where possible ↓ Stool microscopy (× 3) with modified acid-fast and modified trichrome stains + culture + C. difficile toxin ↓ Pathogen identified → specific therapy Blood in stool + CD4 < 50 → suspect CMV colitis → colonoscopy and biopsy → ganciclovir Fever, anaemia, high ALP, CD4 < 50 → suspect MAC → mycobacterial blood culture ↓ Negative studies → endoscopy with duodenal and colonic biopsies ↓ All negative → diagnose HIV enteropathy → optimise ART (the definitive treatment) + symptomatic loperamide/racecadotril + nutritional support |
|
|
Key Treatments ▪ Cryptosporidium — no reliably effective specific drug; nitazoxanide may help; effective ART with immune restoration is the treatment. [VERY HIGH-YIELD] ▪ Cystoisospora and Cyclospora — cotrimoxazole (both treatment and secondary prophylaxis). ▪ Microsporidia — albendazole for Encephalitozoon; fumagillin for Enterocytozoon; ART is key. ▪ CMV colitis — IV ganciclovir or valganciclovir for 21–42 days. ▪ MAC — clarithromycin/azithromycin + ethambutol ± rifabutin. |
|
▪ Oral candidiasis — often accompanies oesophageal disease and supports empirical therapy.
▪ Oesophageal candidiasis — the commonest cause of dysphagia/odynophagia in HIV; retrosternal pain on swallowing; AIDS-defining. [VERY HIGH-YIELD]
▪ CMV oesophagitis — CD4 < 50; single large, deep, well-circumscribed distal ulcer; owl-eye intranuclear inclusions on biopsy.
▪ HSV oesophagitis — multiple small, shallow, "volcano-like" ulcers; Cowdry type A inclusions and multinucleate giant cells.
▪ Idiopathic (aphthous) oesophageal ulcer — large ulcer with no pathogen on biopsy; responds to corticosteroids or thalidomide.
▪ Malignancy — Kaposi sarcoma, lymphoma, oesophageal carcinoma.
▪ Also: pill oesophagitis (zidovudine, doxycycline), reflux disease.
|
Approach to Dysphagia/Odynophagia in HIV Dysphagia or odynophagia in a PLHIV ↓ Empirical fluconazole 200 mg on day 1 then 100–200 mg daily for 14–21 days (especially if oral thrush present) ↓ Improves within 3–7 days → confirms oesophageal candidiasis → complete the course No improvement in 5–7 days → upper GI endoscopy with biopsy and viral culture/histology ↓ Large single deep ulcer → CMV → ganciclovir/valganciclovir Multiple small shallow ulcers → HSV → aciclovir No organism, large ulcer → idiopathic aphthous ulcer → corticosteroids/thalidomide ↓ Start or optimise ART in all cases |
|
Cause |
Typical features |
|
|
Cryptococcal meningitis |
CD4 < 100; subacute headache over days–weeks, fever, vomiting; neck stiffness often ABSENT; raised opening pressure; India ink and CrAg positive [VERY HIGH-YIELD] |
|
|
Tuberculous meningitis |
Subacute; cranial nerve palsies, basal exudates and hydrocephalus on imaging; CSF lymphocytosis, high protein, low glucose, high ADA |
|
|
Bacterial meningitis |
Acute; pneumococcus commonest; neutrophilic CSF with very low glucose |
|
|
Viral meningitis |
Acute HIV itself, HSV, enterovirus; lymphocytic CSF with normal glucose |
|
|
Cerebral toxoplasmosis |
CD4 < 100; headache with focal deficits and seizures; multiple ring-enhancing lesions |
|
|
Primary CNS lymphoma |
CD4 < 50; single (or few) periventricular ring-enhancing lesion; EBV DNA in CSF; thallium-SPECT/PET avid |
|
|
PML |
CD4 < 100; no fever, no headache; progressive focal deficits; non-enhancing white-matter lesions; JC virus PCR in CSF |
|
|
Neurosyphilis |
Any CD4; headache, cranial neuropathies, uveitis, stroke; reactive CSF VDRL |
|
|
Lumbar Puncture and Imaging — Critical Rule [FAVORITE EXAM QUESTION] Perform CT/MRI brain BEFORE lumbar puncture if there is: focal neurological deficit, new-onset seizure, papilloedema, altered sensorium (GCS < 15), or a very low CD4 with focal signs — to exclude a mass lesion and the risk of coning. In cryptococcal meningitis, raised intracranial pressure is common; therapeutic LP with CSF drainage to reduce pressure below 20 cm H₂O is life-saving and must be repeated daily until pressure is controlled. Do not use mannitol, steroids or acetazolamide for this purpose. |
||
▪ Opening pressure (mandatory), cell count and differential, protein, glucose (with paired plasma glucose).
▪ India ink preparation and CSF cryptococcal antigen (CrAg) — CrAg is the most sensitive test (> 95%). [VERY HIGH-YIELD]
▪ Gram stain and bacterial culture; CBNAAT/Xpert MTB/RIF Ultra, AFB smear, mycobacterial culture, CSF ADA.
▪ Fungal culture; CSF VDRL; PCR for JC virus, EBV, HSV, CMV, VZV, toxoplasma.
▪ Cytology and flow cytometry if lymphoma suspected.
|
Management Algorithm — Headache in HIV Headache in a PLHIV ↓ Assess for red flags: fever, altered sensorium, focal deficit, seizure, papilloedema, visual loss ↓ No red flags, CD4 > 200 → treat as tension/migraine; review; still send serum CrAg if CD4 < 200 Red flags present or CD4 < 200 → urgent CT/MRI brain ↓ Mass lesion(s) present → follow the focal-deficit algorithm (section 14.8) No mass lesion → lumbar puncture with opening pressure ↓ CrAg/India ink positive → cryptococcal meningitis → amphotericin B + flucytosine, serial therapeutic LPs, delay ART 4–6 weeks Lymphocytic, high protein, low glucose, high ADA, positive Xpert → TB meningitis → ATT + steroids; delay ART ~4–8 weeks Neutrophilic → bacterial meningitis → ceftriaxone ± vancomycin Reactive CSF VDRL → neurosyphilis → IV penicillin G 18–24 MU/day × 14 days |
|
Cause |
Imaging pattern |
Key discriminator |
|
|
Cerebral toxoplasmosis |
Multiple ring-enhancing lesions in basal ganglia and grey-white junction, marked oedema |
CD4 < 100; Toxoplasma IgG positive; responds to therapy in 10–14 days [VERY HIGH-YIELD] |
|
|
Primary CNS lymphoma |
Single (or few) periventricular ring/homogeneously enhancing lesion, crosses corpus callosum |
CD4 < 50; EBV DNA in CSF; thallium-SPECT/PET avid; no response to anti-toxoplasma therapy |
|
|
Tuberculoma |
Ring-enhancing lesions ± basal meningeal enhancement, hydrocephalus |
Evidence of TB elsewhere; common in India |
|
|
PML |
Non-enhancing, no mass effect, asymmetrical white-matter lesions, subcortical U-fibre involvement |
JC virus PCR in CSF; progressive deficits without fever or headache |
|
|
Stroke |
Vascular territory infarct |
Sudden onset; consider HIV vasculopathy, varicella vasculitis, neurosyphilis, cardioembolism |
|
|
Bacterial / fungal brain abscess |
Ring-enhancing with restricted diffusion on DWI |
Nocardia, Staphylococcus, cryptococcoma, aspergilloma |
|
|
Approach to a Focal Brain Lesion in HIV [FAVORITE EXAM QUESTION] Focal deficit or seizure in a PLHIV → contrast MRI brain (preferred) or CT ↓ Multiple ring-enhancing lesions + Toxoplasma IgG positive + not on cotrimoxazole → empirical anti-toxoplasma therapy (pyrimethamine + sulfadiazine + folinic acid, or cotrimoxazole) for 2 weeks ↓ Reassess clinically and radiologically at 10–14 days ↓ Improvement → continue full induction 6 weeks, then secondary prophylaxis until CD4 > 200 for 6 months on ART No improvement → stereotactic brain biopsy (or CSF EBV DNA + thallium SPECT if biopsy not feasible) → consider primary CNS lymphoma, tuberculoma, PML, abscess ↓ Add anticonvulsants for seizures; dexamethasone only for significant mass effect (it can mask lymphoma histology — avoid before biopsy if possible) ↓ Start or continue ART in all cases |
|||
▪ Biopsy indications: no response to empirical anti-toxoplasma therapy at 2 weeks; single lesion with negative Toxoplasma IgG; atypical imaging; rapid deterioration; diagnostic uncertainty with treatment implications. [IMPORTANT]
▪ HIV-associated neurocognitive disorder (HAND) — a spectrum: asymptomatic neurocognitive impairment (ANI) → mild neurocognitive disorder (MND) → HIV-associated dementia (HAD).
▪ HAD features subcortical dementia — psychomotor slowing, apathy, impaired attention and memory, gait disturbance and tremor, with relative preservation of language. [VERY HIGH-YIELD]
▪ Opportunistic infection — cryptococcal meningitis, TB meningitis, toxoplasmosis, PML, CMV encephalitis, neurosyphilis.
▪ Drug toxicity — efavirenz (chronic neurotoxicity), dolutegravir (insomnia, mood), anticholinergics, benzodiazepines, alcohol.
▪ Metabolic encephalopathy — hepatic, uraemic, hypoglycaemia, hyponatraemia, hypoxia, thyroid disease, B12 deficiency.
▪ Depression — "pseudodementia"; very common and treatable; must be actively excluded.
▪ Substance use — alcohol, cannabis, stimulants, opioids.
▪ Assessment: IHDS or MoCA, MRI brain (diffuse atrophy and symmetrical periventricular white-matter change in HAND), CSF (including HIV RNA for CSF escape), B12, thyroid, syphilis serology.
▪ Management: effective ART is the mainstay; consider CNS-penetrating regimens in documented CSF escape; treat depression and correct metabolic causes; remove offending drugs.
▪ CMV retinitis — CD4 < 50; floaters, painless progressive field loss, "curtain"; perivascular yellow-white retinal necrosis with haemorrhage; sight-threatening. [VERY HIGH-YIELD]
▪ HIV retinopathy — cotton-wool spots; asymptomatic, requires no treatment.
▪ Toxoplasma retinochoroiditis — focal necrotising retinitis with vitritis.
▪ Ocular syphilis — panuveitis, papillitis; treat as neurosyphilis.
▪ Herpes zoster ophthalmicus and acute retinal necrosis — rapidly progressive, may cause bilateral blindness.
▪ Retinal detachment — a late complication of healed CMV retinitis.
▪ Immune recovery uveitis — IRIS in a previously treated CMV retinitis after ART.
|
Urgent Ophthalmology Referral Any visual symptom in a patient with CD4 < 100 is an ophthalmic emergency — same-day dilated fundoscopy. Untreated CMV retinitis causes irreversible blindness within weeks. Start valganciclovir 900 mg twice daily (± intravitreal ganciclovir for sight-threatening zone-1 lesions) and delay ART by ~2 weeks. [IMPORTANT] |
▪ Infectious — herpes zoster and simplex, molluscum contagiosum, dermatophytosis, scabies/crusted scabies, syphilis, bacillary angiomatosis, cryptococcosis, talaromycosis, histoplasmosis, folliculitis and furunculosis.
▪ Inflammatory dermatoses — seborrhoeic dermatitis, psoriasis, pruritic papular eruption, eosinophilic folliculitis, xerosis, atopic eczema.
▪ Neoplasms — Kaposi sarcoma, squamous and basal cell carcinoma, cutaneous lymphoma.
▪ Drug reactions — morbilliform eruption, fixed drug eruption, Stevens-Johnson syndrome/TEN, DRESS; commonest culprits are cotrimoxazole, nevirapine, efavirenz, abacavir and anti-tuberculosis drugs. [VERY HIGH-YIELD]
|
CD4 count |
Characteristic skin conditions |
|
> 500 |
Acute HIV exanthem, seborrhoeic dermatitis, psoriasis |
|
200–500 |
Herpes zoster, oral hairy leukoplakia, dermatophytosis, folliculitis, Kaposi sarcoma |
|
< 200 |
Pruritic papular eruption, extensive molluscum, chronic HSV ulcers, eosinophilic folliculitis |
|
< 100 |
Cutaneous cryptococcosis, talaromycosis, histoplasmosis, bacillary angiomatosis, crusted scabies, disseminated zoster |
▪ Marrow suppression by HIV itself — the commonest cause; normocytic anaemia and cytopenias improve with ART.
▪ Drug toxicity — zidovudine (macrocytic anaemia and neutropenia), cotrimoxazole, ganciclovir, pyrimethamine, amphotericin B, ribavirin, chemotherapy, linezolid. [VERY HIGH-YIELD]
▪ Opportunistic infections infiltrating marrow — disseminated TB, MAC, histoplasmosis, talaromycosis, visceral leishmaniasis, parvovirus B19 (pure red cell aplasia).
▪ Nutritional deficiency — iron, folate, vitamin B12 (also from HIV-related malabsorption).
▪ Haemolysis — autoimmune, drug-induced (dapsone, primaquine in G6PD deficiency), thrombotic microangiopathy.
▪ Immune thrombocytopenia (HIV-ITP) — isolated thrombocytopenia, often at high CD4; responds to ART, then steroids/IVIG if severe. [IMPORTANT]
▪ Lymphoma and other marrow infiltration.
▪ Bone-marrow examination — indicated for unexplained cytopenias, especially with fever; high diagnostic yield for TB, MAC, fungi, leishmania and lymphoma. Send aspirate for culture, AFB, fungal stain and CBNAAT as well as morphology.
▪ HIV-associated nephropathy (HIVAN) — collapsing focal segmental glomerulosclerosis; heavy (often nephrotic-range) proteinuria, normal-sized or large echogenic kidneys, rapid progression; strongly linked to APOL1 risk alleles (African ancestry) and therefore uncommon in India; treatment is ART ± ACE inhibitor ± steroids. [VERY HIGH-YIELD]
▪ HIV immune-complex kidney disease (HIVICK) — IgA nephropathy, membranoproliferative and lupus-like nephritis; relatively more frequent in Indian and Asian cohorts.
▪ Tenofovir (TDF) toxicity — proximal tubulopathy and Fanconi syndrome (glycosuria with normal blood glucose, phosphaturia, hypophosphataemia, hypokalaemia, acidosis), acute tubular necrosis, nephrogenic diabetes insipidus; monitor creatinine, eGFR, urine protein and phosphate. [COMMON MCQ]
▪ Other drug nephrotoxicity — indinavir/atazanavir crystalluria and stones, amphotericin B, aminoglycosides, aciclovir, cotrimoxazole, foscarnet, NSAIDs.
▪ Thrombotic microangiopathy (HIV-TTP) — microangiopathic haemolytic anaemia, thrombocytopenia, renal failure, fever, neurological signs; requires plasma exchange.
▪ Opportunistic infection of the kidney — TB (sterile pyuria, renal calcification), CMV, cryptococcus.
▪ Diabetes and hypertension — increasingly the leading causes of CKD in ageing PLHIV.
▪ Evaluation: creatinine/eGFR, urinalysis, urine protein-creatinine ratio, serum phosphate and potassium, renal ultrasound, and renal biopsy if proteinuria > 1 g/day or unexplained renal failure.
▪ Hepatitis B — chronic HBV coinfection; ART must include tenofovir + lamivudine; withdrawal precipitates a flare. [VERY HIGH-YIELD]
▪ Hepatitis C — high prevalence in PWID; curable with direct-acting antivirals; check for drug interactions with ART.
▪ Drug-induced liver injury — nevirapine (hypersensitivity hepatitis in the first 12 weeks, especially in women with CD4 > 250), efavirenz, protease inhibitors, maraviroc, cotrimoxazole, azoles, statins.
▪ Anti-tuberculosis drugs — isoniazid, rifampicin and pyrazinamide are the commonest cause of hepatotoxicity in Indian PLHIV; stop ATT if ALT > 5 × ULN, or > 3 × ULN with symptoms/jaundice. [IMPORTANT]
▪ Opportunistic infection — disseminated TB and MAC (raised alkaline phosphatase with fever), CMV, histoplasmosis, cryptococcosis; AIDS cholangiopathy (cryptosporidium, CMV, microsporidia) causing marked ALP rise with biliary pain.
▪ Metabolic dysfunction-associated fatty liver disease — increasingly common with ART-related weight gain (especially INSTIs and TAF).
▪ Alcohol-related liver disease.
▪ Others: nodular regenerative hyperplasia (didanosine), lactic acidosis with hepatic steatosis (older NRTIs), atazanavir/indinavir unconjugated hyperbilirubinaemia (benign, dose-related, resembles Gilbert syndrome). [COMMON MCQ]
▪ Evaluation pattern: predominantly cholestatic (high ALP/GGT) → TB, MAC, AIDS cholangiopathy, drugs, infiltration; predominantly hepatocellular (high ALT/AST) → viral hepatitis, drug injury, alcohol, fatty liver.
▪ Fever — infection (usually TB in India), malignancy, drug fever, IRIS, HIV itself.
▪ Fatigue — anaemia, depression, hypothyroidism, hypogonadism, adrenal insufficiency, chronic infection, drug effect.
▪ Weight loss and wasting — see section 14.2; HIV wasting syndrome is AIDS-defining.
▪ Night sweats — classically TB, lymphoma, MAC, histoplasmosis.
▪ Infective dermatoses — herpes zoster/simplex, molluscum, dermatophytosis, scabies, syphilis, bacterial folliculitis, bacillary angiomatosis, deep mycoses.
▪ Inflammatory dermatoses — seborrhoeic dermatitis, psoriasis, pruritic papular eruption, eosinophilic folliculitis, xerosis, prurigo nodularis.
▪ Neoplasms — Kaposi sarcoma, non-melanoma skin cancer, cutaneous lymphoma.
▪ Drug reactions — morbilliform, SJS/TEN, DRESS, fixed drug eruption.
▪ Hair changes — diffuse thinning, premature greying, straightening; alopecia areata; eyelash trichomegaly (advanced disease).
▪ Nail changes — onychomycosis, longitudinal melanonychia (zidovudine), clubbing, yellow nail syndrome.
▪ Pigmentary changes — diffuse or mucocutaneous hyperpigmentation, vitiligo, post-inflammatory pigmentation of PPE.
▪ Candidiasis — pseudomembranous, erythematous, hyperplastic, angular cheilitis.
▪ Oral hairy leukoplakia — EBV, lateral tongue, non-scrapable. [FAVORITE EXAM QUESTION]
▪ Aphthous ulcers — minor, major and herpetiform; major ulcers may be disabling.
▪ Periodontal disease — linear gingival erythema, necrotising ulcerative gingivitis and periodontitis.
▪ Salivary-gland disease — DILS, lymphoepithelial cysts, xerostomia.
▪ HSV — recurrent herpes labialis and intraoral ulcers; HPV — oral warts.
▪ Kaposi sarcoma — hard palate and gingiva; non-Hodgkin lymphoma — palatal or gingival mass.
▪ Opportunistic infections — PCP, cryptococcosis, histoplasmosis, talaromycosis, aspergillosis, nocardiosis, CMV.
▪ Recurrent bacterial pneumonia — ≥ 2 episodes in 12 months is AIDS-defining; pneumococcus most common; vaccination is essential.
▪ Tuberculosis — the commonest HIV-associated respiratory disease worldwide and in India.
▪ Bronchiectasis — from recurrent infection and lymphoid interstitial pneumonitis in children.
▪ COPD — accelerated by smoking, recurrent infection and HIV-related inflammation.
▪ Pulmonary hypertension — HIV-associated PAH; incidence far above the general population; treat with ART plus PAH-specific therapy.
▪ Lung cancer — 2–3 times higher incidence, largely but not entirely attributable to smoking; presents younger and at more advanced stage. [IMPORTANT]
▪ Oesophagitis — candida, CMV, HSV, idiopathic ulcer, pill oesophagitis.
▪ HIV enteropathy — villous atrophy, malabsorption; diagnosis of exclusion.
▪ Diarrhoea — infectious, drug-related and neoplastic causes (section 14.5).
▪ Malabsorption — small-bowel infection, pancreatic insufficiency, mucosal atrophy.
▪ Hepatobiliary disease — HBV, HCV, drug injury, fatty liver, opportunistic infection, acalculous cholecystitis.
▪ Pancreatitis — didanosine, stavudine, pentamidine, cotrimoxazole, hypertriglyceridaemia (PIs), CMV, alcohol.
▪ AIDS cholangiopathy — papillary stenosis and sclerosing cholangitis due to cryptosporidium, CMV or microsporidia; marked ALP elevation with right upper quadrant pain; ERCP with sphincterotomy relieves pain. [VERY HIGH-YIELD]
▪ Anorectal disease — proctitis, fissures, fistulae, HPV-related dysplasia and carcinoma.
▪ Hepatitis B — accelerated fibrosis, higher HBV DNA, lower seroconversion; ART must be HBV-active; hepatocellular carcinoma surveillance required.
▪ Hepatitis C — faster progression to cirrhosis; DAAs give > 95% cure irrespective of HIV status.
▪ Drug-induced liver injury — ART and anti-TB drugs; the commonest hepatic problem in Indian practice.
▪ Fatty liver disease — obesity, dyslipidaemia, diabetes, ART-related weight gain.
▪ Opportunistic infections — granulomatous hepatitis of TB and MAC, fungal infection, CMV.
▪ Portal hypertension — cirrhotic, and non-cirrhotic portal hypertension associated with didanosine (nodular regenerative hyperplasia).
▪ Meningitis — cryptococcal, tuberculous, bacterial, syphilitic, aseptic (acute HIV).
▪ Encephalitis — CMV, HSV, VZV, toxoplasma, HIV itself.
▪ CNS opportunistic infections — toxoplasmosis, PML, tuberculoma, cryptococcoma, nocardial abscess.
▪ HIV-associated neurocognitive disorder — ANI, MND, HIV-associated dementia (subcortical pattern).
▪ Vacuolar myelopathy — progressive spastic paraparesis, sensory ataxia, sphincter disturbance; no sensory level; vacuolation of dorsal and lateral columns resembling subacute combined degeneration. [COMMON MCQ]
▪ Distal symmetrical polyneuropathy — the commonest neurological complication; painful burning feet; from HIV, stavudine/didanosine, isoniazid, B12 deficiency.
▪ Mononeuropathy multiplex — vasculitic, CMV-related in advanced disease.
▪ Inflammatory demyelinating neuropathy — AIDP/CIDP, typically at seroconversion or higher CD4.
▪ Myopathy — HIV myositis, zidovudine mitochondrial myopathy (ragged red fibres), statin interaction.
▪ Stroke — HIV vasculopathy, VZV vasculitis, neurosyphilis, cardioembolism, accelerated atherosclerosis, cocaine use.
▪ Seizures — from mass lesions, meningitis, metabolic causes; note interactions between enzyme-inducing anticonvulsants and ART.
▪ Depression — the commonest psychiatric disorder in PLHIV (2–4 times general population); a major cause of non-adherence. [VERY HIGH-YIELD]
▪ Anxiety disorders and adjustment disorder — especially at diagnosis, disclosure and treatment failure.
▪ Psychosis — HIV-related, drug-induced (efavirenz, steroids), substance-induced, or from CNS opportunistic infection.
▪ Substance-use disorders — alcohol, opioids, stimulants; both cause and consequence of risk behaviour.
▪ Suicide risk — significantly elevated; ask directly, especially at diagnosis and after bad news. [IMPORTANT]
▪ Cognitive disorder — HAND; must be distinguished from depression.
▪ Note drug interactions: many antidepressants and antipsychotics interact with PIs (avoid pimozide); efavirenz may worsen mood and sleep.
▪ Cardiomyopathy — dilated cardiomyopathy from HIV, nutritional deficiency (selenium, thiamine), myocarditis, drugs.
▪ Pericardial effusion — TB is the commonest cause in India; may cause tamponade or constriction.
▪ Myocarditis — HIV, CMV, toxoplasma, coxsackie.
▪ Infective endocarditis — right-sided S. aureus in PWID; also Salmonella and fungal endocarditis.
▪ Pulmonary hypertension — HIV-associated PAH.
▪ Premature atherosclerosis — 1.5–2 fold higher myocardial infarction risk from chronic inflammation, dyslipidaemia (PIs), smoking and traditional risk factors; use statins liberally (with interaction checks). [VERY HIGH-YIELD]
▪ Venous thromboembolism — 2–10 fold higher risk, related to inflammation, protein S deficiency and infection.
▪ HIV-associated nephropathy (collapsing FSGS), HIV immune-complex disease, thrombotic microangiopathy.
▪ Drug nephrotoxicity — tenofovir (Fanconi, tubulopathy), indinavir/atazanavir stones, amphotericin, aminoglycosides, cotrimoxazole (raises creatinine by blocking tubular secretion without true GFR fall).
▪ Electrolyte disorders — hyponatraemia (SIADH from pneumonia/CNS infection, adrenal insufficiency), hypokalaemia and hypophosphataemia (tenofovir tubulopathy), hyperkalaemia (cotrimoxazole, ACE inhibitors).
▪ Chronic kidney disease — increasing with age, diabetes, hypertension and long-term tenofovir exposure.
▪ Anaemia — the commonest haematological abnormality; multifactorial; an independent predictor of mortality.
▪ Neutropenia — HIV, zidovudine, cotrimoxazole, ganciclovir; increases bacterial infection risk.
▪ Thrombocytopenia — HIV-ITP, marrow infiltration, TTP, drugs, hypersplenism.
▪ Pancytopenia — disseminated TB, MAC, histoplasmosis, visceral leishmaniasis, lymphoma, marrow infiltration, drugs.
▪ Haemolysis — autoimmune, G6PD deficiency with dapsone/primaquine, TTP.
▪ Coagulopathy — lupus anticoagulant (usually not thrombogenic), liver disease, DIC in sepsis.
▪ Thrombosis — increased venous thromboembolism risk; protein S deficiency common.
▪ Marrow infiltration — lymphoma, mycobacteria, fungi, leishmania.
▪ Adrenal insufficiency — CMV adrenalitis, TB adrenals, ketoconazole, rifampicin (accelerated steroid metabolism), megestrol withdrawal; suspect with hyponatraemia, hyperkalaemia, hypotension, fatigue. [IMPORTANT]
▪ Hypogonadism — common in advanced disease; fatigue, low libido, loss of muscle mass.
▪ Thyroid disease — subclinical hypothyroidism; Graves disease as an immune-reconstitution phenomenon months to years after ART. [COMMON MCQ]
▪ Diabetes and insulin resistance — protease inhibitors, weight gain with INSTIs, hepatitis C.
▪ Dyslipidaemia — raised triglycerides and LDL with low HDL; PIs and efavirenz.
▪ Lipodystrophy — peripheral lipoatrophy (thymidine analogues) with central fat accumulation.
▪ Lactic acidosis — from mitochondrial toxicity of stavudine/didanosine/zidovudine; nausea, weight loss, dyspnoea, hepatomegaly; potentially fatal.
▪ Osteopenia and osteoporosis — 3-fold higher; HIV itself, tenofovir, PIs, vitamin D deficiency, low BMI, smoking.
▪ Vitamin D deficiency — highly prevalent; worsened by efavirenz.
▪ Arthralgia — the commonest rheumatological complaint.
▪ HIV-associated arthritis — oligoarticular, self-limiting, seronegative.
▪ Reactive arthritis — asymmetrical lower-limb oligoarthritis with enthesitis, urethritis, conjunctivitis; often severe in HIV; HLA-B27 associated.
▪ Psoriatic arthritis — may be explosive in onset with severe skin disease.
▪ Myositis — HIV polymyositis, pyomyositis (S. aureus, common in the tropics), zidovudine myopathy.
▪ Vasculitis — HIV-associated, polyarteritis-like, or cryoglobulinaemic with HCV coinfection.
▪ Sicca syndrome — dry eyes and mouth resembling Sjögren but CD8-predominant and anti-Ro/La negative.
▪ Diffuse infiltrative lymphocytosis syndrome (DILS) — CD8 lymphocytosis with parotid enlargement, sicca symptoms, lymphocytic interstitial pneumonitis and neuropathy; responds to ART. [FAVORITE EXAM QUESTION]
▪ Avascular necrosis of the femoral head — increased risk with steroids, PIs and hyperlipidaemia.
▪ Menstrual abnormalities — amenorrhoea, oligomenorrhoea; related to weight loss, chronic illness and drugs.
▪ Infertility — tubal damage from PID/STI, low semen quality, chronic illness.
▪ Sexual dysfunction — erectile dysfunction, low libido; hypogonadism, depression, drugs, stigma.
▪ Contraception — condoms always (dual protection); note that efavirenz and PIs reduce the efficacy of hormonal contraceptives; DMPA, IUCD and implants are safe options (implants have reduced levels with efavirenz). [IMPORTANT]
▪ Pregnancy planning — achieve viral suppression before conception; U = U allows safe conception in serodiscordant couples; alternatives are timed unprotected intercourse with PrEP or assisted reproduction.
▪ Cervical disease — accelerated HPV-related CIN and invasive carcinoma; screen at diagnosis and annually.
▪ Anal disease — anal HPV infection, AIN and carcinoma; screen high-risk groups.
▪ Menopause — occurs earlier in women with HIV; increases osteoporosis and cardiovascular risk.
|
The Standard OI Template — Use This For Every Organism [IMPORTANT] 1. Etiology — organism and its microbiological characteristics. 2. Epidemiology — global and Indian distribution, endemic areas. 3. CD4 association — the threshold below which the infection occurs. 4. Pathogenesis — primary infection versus reactivation of latent infection. 5. Clinical features — organ involvement and typical presentation. 6. Investigations and diagnosis — the confirmatory test. 7. Differential diagnosis. 8. Treatment — induction → consolidation → maintenance (secondary prophylaxis), with drug, dose and duration. 9. Adverse effects and drug interactions. 10. Timing of ART and risk of IRIS. 11. Primary and secondary prophylaxis — when to start, when to stop, when to restart. 12. Relapse and prognosis. |
||
|
CD4 threshold |
Opportunistic infections that become likely |
|
|
Any CD4 |
Tuberculosis, bacterial pneumonia, herpes zoster, syphilis, non-typhoidal salmonellosis |
|
|
< 250 |
Coccidioidomycosis, eosinophilic folliculitis |
|
|
< 200 |
Pneumocystis pneumonia, oesophageal candidiasis, disseminated/miliary TB, cryptosporidiosis |
|
|
< 150 |
Disseminated histoplasmosis, talaromycosis |
|
|
< 100 |
Cerebral toxoplasmosis, cryptococcal meningitis, chronic HSV ulceration, microsporidiosis |
|
|
< 50 |
CMV retinitis/colitis, disseminated MAC, primary CNS lymphoma, PML [VERY HIGH-YIELD] |
|
|
Universal Principles of OI Management [VERY HIGH-YIELD] ▪ Effective ART is the single most important intervention — it prevents and cures most OIs by restoring immunity. ▪ Secondary prophylaxis (maintenance therapy) continues until CD4 recovery is documented and sustained (usually CD4 > 100–200 for ≥ 6 months with viral suppression). ▪ Restart prophylaxis if CD4 falls below the threshold again. ▪ ART timing: start within 2 weeks for most OIs, except cryptococcal meningitis (delay 4–6 weeks) and TB meningitis (delay ~4–8 weeks), where early ART increases mortality from IRIS. ▪ Always screen for TB before starting ART in India. |
||
|
The Single Most Important OI in India [VERY HIGH-YIELD] ▪ TB is the commonest opportunistic infection and the commonest cause of death in Indian PLHIV. ▪ HIV increases the lifetime risk of TB from ~10% to ~10% per year. ▪ TB occurs at any CD4 count — unlike almost every other OI. ▪ Every PLHIV must be screened for TB at every clinical visit using the four-symptom screen: current cough, fever, weight loss, night sweats. |
▪ Mycobacterium tuberculosis — acid-fast bacillus; India has the world's largest TB burden.
▪ ~3–5% of notified TB patients in India are HIV-positive; ~10% of PLHIV develop TB annually if untreated.
▪ TB occurs at all CD4 counts; extrapulmonary and disseminated forms increase as CD4 falls.
|
Feature |
CD4 > 350 (preserved immunity) |
CD4 < 200 (advanced) |
|
Site |
Predominantly pulmonary |
Frequently extrapulmonary and disseminated |
|
Chest X-ray |
Upper-lobe infiltrate with cavitation |
Lower/mid-zone infiltrate, miliary, mediastinal nodes, effusion; may be normal in up to 20% |
|
Sputum smear |
Usually positive |
Frequently negative (paucibacillary) |
|
Tuberculin test |
May be positive |
Usually negative (anergy) |
|
Presentation |
Classic cough, sweats, weight loss |
Non-specific fever, wasting; sepsis-like [FAVORITE EXAM QUESTION] |
▪ Pulmonary TB — commonest form at all CD4 counts.
▪ Extrapulmonary TB — lymph node (commonest EPTB, cervical), pleural, pericardial, abdominal, meningeal, spinal, genitourinary, cutaneous; extrapulmonary TB is an AIDS-defining illness.
▪ Disseminated (miliary) TB — fever, wasting, hepatosplenomegaly, pancytopenia; may present as mycobacteraemia and sepsis in profound immunosuppression.
▪ CBNAAT (Xpert MTB/RIF) or Truenat — the first-line diagnostic test for all presumptive TB in PLHIV; simultaneously detects rifampicin resistance. [VERY HIGH-YIELD]
▪ Urine LF-LAM (lateral flow lipoarabinomannan) — recommended when CD4 < 200, WHO stage 3/4 or seriously ill; rapid, useful in disseminated disease and smear-negative patients. [IMPORTANT]
▪ Sputum smear microscopy and liquid culture (MGIT) with drug-susceptibility testing.
▪ Chest radiograph — remember it may be normal or atypical.
▪ Extrapulmonary samples — FNAC/biopsy of nodes with CBNAAT, pleural/pericardial/ascitic fluid with ADA and CBNAAT, CSF Xpert MTB/RIF Ultra.
▪ Blood culture for mycobacteria in disseminated disease; bone-marrow aspirate/biopsy.
▪ Line probe assay (LPA) for first- and second-line drug resistance.
▪ Intensive phase (2 months): Isoniazid + Rifampicin + Pyrazinamide + Ethambutol (HRZE), daily, weight-band dosed fixed-dose combination.
▪ Continuation phase (4 months): Isoniazid + Rifampicin + Ethambutol (HRE), daily.
▪ Total duration 6 months for most; extended to 9–12 months for CNS and osteoarticular TB, and 6–9 months in some disseminated forms.
▪ Pyridoxine 10–25 mg daily must be added to prevent isoniazid neuropathy in all PLHIV. [IMPORTANT]
▪ Steroids — indicated in TB meningitis and TB pericarditis (dexamethasone/prednisolone tapered over 6–8 weeks).
▪ MDR-TB — resistance to isoniazid and rifampicin; treated per NTEP with all-oral regimens containing bedaquiline, linezolid, levofloxacin/moxifloxacin, clofazimine and cycloserine; shorter (BPaLM) regimens where eligible.
▪ Note additive toxicities in HIV: linezolid (myelosuppression, neuropathy), bedaquiline and moxifloxacin (QT prolongation), cycloserine (psychiatric effects). ECG monitoring is essential. [IMPORTANT]
|
Rifampicin and ART [FAVORITE EXAM QUESTION] Rifampicin is a powerful CYP3A4 and UGT1A1 inducer that reduces the levels of most antiretrovirals. ▪ Dolutegravir: give 50 mg TWICE daily while on rifampicin, and continue for 2 weeks after stopping it. ▪ Efavirenz: no dose change needed — the historically preferred partner with rifampicin. ▪ Protease inhibitors: contraindicated with rifampicin; substitute rifabutin 150 mg daily (rifabutin is a much weaker inducer but its own level rises with PIs). ▪ Bictegravir, rilpivirine and TAF-containing regimens: avoid with rifampicin. ▪ Rifampicin also lowers levels of azoles, methadone, oral contraceptives, warfarin, steroids and many others. |
|
Situation |
When to start ART |
|
CD4 < 50 (non-meningeal TB) |
Within 2 weeks of starting ATT [VERY HIGH-YIELD] |
|
CD4 ≥ 50 (non-meningeal TB) |
Within 8 weeks (usually by 2–8 weeks) |
|
TB meningitis |
Delay ART to ~4–8 weeks; early ART increases severe adverse events and mortality |
|
Pregnancy with TB |
As early as possible, regardless of CD4 |
▪ Paradoxical TB-IRIS — worsening of already-treated TB after ART: recurrent fever, enlarging nodes, worsening infiltrates, new effusions, expanding CNS lesions.
▪ Unmasking TB-IRIS — previously subclinical TB becomes florid after ART.
▪ Risk factors: CD4 < 50, disseminated TB, short interval between ATT and ART, high pre-ART viral load.
▪ Management: continue both ATT and ART; NSAIDs for mild disease; prednisolone 1.5 mg/kg/day tapered over 4 weeks for moderate-severe disease; drain collections; exclude drug resistance, treatment failure and a new infection before diagnosing IRIS. [IMPORTANT]
▪ Offer to all PLHIV in whom active TB has been excluded, irrespective of CD4 count and ART status.
▪ Regimens: isoniazid 300 mg daily for 6 months (6H) — the NTEP standard; alternatives 3HP (weekly isoniazid + rifapentine × 12 doses) and 3HR.
▪ Add pyridoxine; check for hepatitis and neuropathy; note rifapentine/rifampicin interactions with ART (3HP is compatible with dolutegravir at standard dose).
▪ TPT reduces TB incidence and mortality additively with ART. [VERY HIGH-YIELD]
▪ Mortality is highest in the first 2 months of therapy, in disseminated disease and with CD4 < 50.
▪ Cure rates with adherent therapy and ART approach those in HIV-negative TB.
▪ AIDS-defining if ≥ 2 episodes within 12 months. [COMMON MCQ]
▪ Commonest organisms: Streptococcus pneumoniae (most frequent), Haemophilus influenzae, Staphylococcus aureus, Klebsiella, Pseudomonas (advanced disease).
▪ Risk relates to B-cell dysfunction and impaired opsonisation; occurs at any CD4 but rises as CD4 falls.
▪ Presentation: acute fever, productive cough, pleuritic pain, focal consolidation; bacteraemia is more common than in HIV-negative persons.
▪ Treatment: as for community-acquired pneumonia — amoxicillin-clavulanate + macrolide, or ceftriaxone + azithromycin; escalate for severe disease.
▪ Prevention: ART, pneumococcal vaccination (PCV followed by PPSV23), influenza vaccination, smoking cessation; cotrimoxazole prophylaxis provides partial protection. [IMPORTANT]
▪ Salmonella Typhimurium and Enteritidis; recurrent bacteraemia is AIDS-defining.
▪ CD4 usually < 200; presents with fever and bacteraemia, often without diarrhoea. [IMPORTANT]
▪ Diagnosis by blood culture (repeatedly positive) and stool culture.
▪ Treatment: ciprofloxacin or ceftriaxone for 2–6 weeks; secondary prophylaxis with ciprofloxacin for recurrent disease until immune reconstitution.
▪ Prevention: food and water hygiene; ART.
▪ Nocardia asteroides complex, N. brasiliensis — aerobic, branching, filamentous, weakly/modified acid-fast Gram-positive bacteria. [FAVORITE EXAM QUESTION]
▪ CD4 usually < 100; acquired by inhalation from soil.
▪ Clinical: subacute pneumonia with upper-lobe cavitation (mimics TB), and haematogenous spread to the brain (abscess) and skin.
▪ Diagnosis: modified Kinyoun/Ziehl-Neelsen stain of sputum, BAL or abscess pus; culture (requires prolonged incubation — inform the laboratory).
▪ Treatment: high-dose cotrimoxazole ± imipenem/amikacin for severe or CNS disease; total duration 6–12 months (12 months for CNS disease) to prevent relapse.
▪ Bartonella henselae (cat exposure/cat scratch) and Bartonella quintana (body louse, homelessness).
▪ CD4 usually < 100.
▪ Bacillary angiomatosis — friable, red-purple vascular papules and nodules that bleed easily; closely mimics Kaposi sarcoma — the key distinction is that bacillary angiomatosis is curable with antibiotics. [VERY HIGH-YIELD]
▪ Systemic forms: peliosis hepatis (blood-filled hepatic cysts), bacteraemia with fever, osteomyelitis, endocarditis (culture-negative).
▪ Diagnosis: skin biopsy with Warthin-Starry silver stain showing bacilli; PCR; serology; prolonged blood culture.
▪ Treatment: erythromycin or doxycycline for at least 3 months (4 months for bone/visceral disease); may relapse if stopped early. Avoid Jarisch-Herxheimer-like reaction by monitoring in severe disease.
▪ Treponema pallidum; strongly epidemiologically linked to HIV — each facilitates the other.
▪ Presentation in HIV may be atypical: multiple or persistent chancres, overlapping primary and secondary stages, more aggressive course, lues maligna (ulceronodular syphilis), and earlier neurological involvement. [VERY HIGH-YIELD]
▪ Serology is usually reliable, but can show unusually high titres, delayed reactivity, or the prozone phenomenon (false-negative undiluted VDRL in very high titre disease). [COMMON MCQ]
▪ Indications for lumbar puncture: neurological, ocular or auditory symptoms; tertiary syphilis; serological failure after adequate therapy.
▪ Treatment: early syphilis — benzathine penicillin G 2.4 MU IM single dose; late latent/unknown duration — 2.4 MU IM weekly × 3.
▪ Neurosyphilis (and ocular/otic syphilis): aqueous crystalline penicillin G 18–24 million units/day IV for 10–14 days — this is the correct treatment for ocular syphilis even without CSF abnormalities. [FAVORITE EXAM QUESTION]
▪ Follow-up: repeat non-treponemal titres at 3, 6, 9, 12 and 24 months; expect a 4-fold fall. Penicillin-allergic patients should be desensitised rather than given alternatives, especially in pregnancy and neurosyphilis.
▪ Jarisch-Herxheimer reaction — fever, chills and myalgia within hours of treatment; manage with antipyretics; warn pregnant women (risk of fetal distress).
▪ Listeria monocytogenes — Gram-positive, facultative intracellular, motile ("tumbling motility"), grows at 4 °C (cold enrichment).
▪ Risk from unpasteurised dairy, soft cheese, deli meats and contaminated vegetables; CD4 usually < 100.
▪ Clinical: meningitis (often with brainstem involvement — rhombencephalitis), bacteraemia; in pregnancy causes fetal loss and neonatal sepsis.
▪ Treatment: ampicillin (± gentamicin); cotrimoxazole in penicillin allergy. Cephalosporins are ineffective — a classic examination point. [VERY HIGH-YIELD]
▪ Prevention: food-safety advice; cotrimoxazole prophylaxis provides partial protection.
▪ Rhodococcus equi — Gram-positive, partially acid-fast, intracellular coccobacillus; associated with exposure to horses, livestock and soil.
▪ CD4 usually < 100.
▪ Clinical: indolent cavitating upper-lobe pneumonia with abscess formation, closely mimicking tuberculosis and nocardiosis; may disseminate to brain and bone.
▪ Diagnosis: culture of sputum, blood or abscess; histology shows malakoplakia with Michaelis-Gutmann bodies.
▪ Treatment: combination therapy with vancomycin or imipenem plus a macrolide/rifampicin/fluoroquinolone for weeks, then oral suppression until immune reconstitution; surgical drainage may be needed. Relapse is common.
▪ Mycobacterium avium and M. intracellulare — ubiquitous environmental mycobacteria in soil, water and food.
▪ Acquired by inhalation and ingestion; disease represents primary infection rather than reactivation.
▪ Occurs almost exclusively at CD4 < 50 cells/µL. [VERY HIGH-YIELD]
▪ Much less commonly reported in India than in Western cohorts, partly because patients die of TB first and partly because of under-diagnosis.
▪ Disseminated MAC: persistent fever, drenching night sweats, weight loss, fatigue, chronic diarrhoea and abdominal pain.
▪ Hepatosplenomegaly and intra-abdominal (retroperitoneal, mesenteric) lymphadenopathy.
▪ Laboratory clues: severe anaemia out of proportion to illness and a markedly raised alkaline phosphatase. [FAVORITE EXAM QUESTION]
▪ Localised MAC as IRIS — focal suppurative lymphadenitis, especially cervical or abdominal, after ART.
▪ Mycobacterial blood culture — the diagnostic test of choice for disseminated disease. [IMPORTANT]
▪ Culture of bone marrow, lymph node, liver biopsy or stool; acid-fast bacilli on smear of these tissues.
▪ Histology shows foamy macrophages packed with acid-fast bacilli and poorly formed granulomas (contrast with the well-formed caseating granulomas of TB).
▪ Differentiation from TB is essential — MAC is resistant to standard anti-tuberculosis drugs.
▪ Induction/definitive therapy: clarithromycin 500 mg twice daily (or azithromycin 500–600 mg daily) + ethambutol 15 mg/kg daily; add a third drug (rifabutin 300 mg daily, or amikacin/a fluoroquinolone) in severe disease or high mycobacterial load.
▪ Duration: at least 12 months, and continue until CD4 > 100 cells/µL for ≥ 6 months on ART with resolution of symptoms.
▪ Adverse effects and interactions: clarithromycin (GI upset, QT prolongation, taste disturbance; interacts with PIs and rifabutin), ethambutol (optic neuritis — check colour vision), rifabutin (uveitis, neutropenia; dose adjustment with PIs).
▪ Start ART after ~2 weeks of MAC therapy.
▪ MAC-IRIS — fever with focal suppurative lymphadenitis; manage with continued therapy, drainage and steroids if severe.
▪ Primary prophylaxis (azithromycin 1200 mg weekly at CD4 < 50) is no longer routinely recommended where ART is promptly available and active TB has been excluded; it is not part of standard Indian practice. [IMPORTANT]
▪ Secondary prophylaxis = continuation of the treatment regimen; stop when CD4 > 100 for ≥ 6 months and ≥ 12 months of therapy completed; restart if CD4 falls below 100.
▪ Prognosis is good with combined MAC therapy and ART; untreated disseminated MAC has a median survival of only a few months.
▪ M. kansasii — pulmonary disease resembling TB with thin-walled cavities; treat with isoniazid + rifampicin + ethambutol.
▪ M. genavense — disseminated disease with GI involvement; difficult to culture.
▪ M. haemophilum — skin nodules, ulcers, arthritis; requires iron-supplemented media at low temperature.
▪ Rapid growers (M. abscessus, M. fortuitum, M. chelonae) — skin, soft-tissue and catheter-related infection; often highly drug-resistant, requiring macrolide plus amikacin/imipenem combinations.
▪ M. scrofulaceum — cervical lymphadenitis.
▪ General principle: NTM require species identification and susceptibility testing; regimens differ from those for M. tuberculosis, and treatment continues until immune reconstitution. [IMPORTANT]
▪ Pneumocystis jirovecii — an atypical fungus (formerly classified as a protozoon) that cannot be cultured; transmitted by the airborne route. [COMMON MCQ]
▪ The commonest AIDS-defining OI in the West; less common but definitely present in India, where it is often misdiagnosed as smear-negative TB.
▪ CD4 < 200 cells/µL — the classic threshold for both disease and prophylaxis. [VERY HIGH-YIELD]
▪ Organisms attach to type I alveolar pneumocytes → alveolar inflammation, foamy exudate and impaired gas exchange without airway destruction.
▪ Classic triad: subacute progressive exertional dyspnoea, non-productive dry cough and fever developing over days to weeks.
▪ Examination is often near-normal — chest may be clear despite marked hypoxaemia; exertional desaturation is the key bedside finding. [FAVORITE EXAM QUESTION]
▪ Extrapulmonary pneumocystosis is rare (associated with aerosolised pentamidine prophylaxis).
▪ Chest radiograph: bilateral perihilar/diffuse interstitial ground-glass infiltrates, classically sparing the apices; may be normal early. Pneumatoceles and pneumothorax are characteristic complications.
▪ HRCT chest: patchy or geographic ground-glass opacification with cyst formation — high sensitivity when the film is normal.
▪ Serum LDH markedly raised (sensitive, not specific); serum β-D-glucan raised.
▪ ABG — hypoxaemia with raised A-a gradient; exercise oximetry shows desaturation.
▪ Definitive diagnosis: demonstration of the organism in induced sputum or bronchoalveolar lavage using Grocott methenamine silver, toluidine blue or Giemsa stain, direct immunofluorescence, or PCR. Cysts are 4–7 µm with intracystic bodies. [VERY HIGH-YIELD]
▪ Tuberculosis (especially miliary), viral pneumonitis (CMV, influenza, COVID-19), bacterial atypical pneumonia, pulmonary oedema, lymphocytic interstitial pneumonitis, drug-induced pneumonitis.
▪ First line: cotrimoxazole (TMP-SMX) 15–20 mg/kg/day of trimethoprim in 3–4 divided doses, IV in severe disease, oral in mild-moderate; total 21 days. [VERY HIGH-YIELD]
▪ Adjunctive corticosteroids if PaO₂ < 70 mmHg on room air or A-a gradient > 35 mmHg — prednisolone 40 mg BD × 5 days → 40 mg OD × 5 days → 20 mg OD × 11 days; must start within 72 hours of cotrimoxazole.
▪ Alternatives: clindamycin + primaquine (check G6PD); IV pentamidine; atovaquone (mild disease); trimethoprim + dapsone.
▪ Adverse effects of cotrimoxazole: rash (including SJS/TEN), fever, nausea, cytopenias, hyperkalaemia, hepatitis, and a rise in serum creatinine without a true GFR fall (blocked tubular secretion). Desensitisation is possible for mild rash. [IMPORTANT]
▪ Start ART within 2 weeks of beginning PCP treatment — early ART reduces mortality.
▪ PCP-IRIS — paradoxical worsening with fever and hypoxia; manage with steroids and continued therapy.
▪ Primary prophylaxis: cotrimoxazole 1 DS (960 mg) daily (or single strength daily) when CD4 < 200, oropharyngeal candidiasis present, WHO stage 3/4, or CD4% < 14. Alternatives: dapsone, atovaquone, aerosolised pentamidine.
▪ Secondary prophylaxis: same regimen after treatment.
▪ Stop prophylaxis when CD4 > 200 for ≥ 3–6 months on ART; restart if CD4 falls below 200. [VERY HIGH-YIELD]
▪ Note: cotrimoxazole simultaneously protects against toxoplasmosis, isosporiasis, nocardiosis, many bacterial infections and malaria — a major reason it is given universally at CD4 < 200 in India.
▪ Prognosis: mortality 10–20% overall, higher with delayed treatment, mechanical ventilation and pneumothorax.
▪ Cryptococcus neoformans — encapsulated yeast acquired by inhalation from soil contaminated with pigeon droppings; C. gattii infects immunocompetent hosts and is associated with eucalyptus trees.
▪ The commonest cause of adult meningitis in high-HIV-burden settings, and a leading cause of AIDS mortality.
▪ CD4 < 100 cells/µL (usually < 50). [VERY HIGH-YIELD]
▪ Subacute onset over days to weeks: headache, fever, malaise, nausea and vomiting.
▪ Meningism is frequently ABSENT — a normal neck does not exclude cryptococcal meningitis. [FAVORITE EXAM QUESTION]
▪ Features of raised intracranial pressure: severe headache, vomiting, papilloedema, visual loss, VI nerve palsy, confusion and coma.
▪ Extrameningeal disease: pulmonary cryptococcosis (nodules, cavities), umbilicated molluscum-like skin papules, lymphadenopathy, fungaemia, prostatic and bone involvement.
▪ Serum/plasma cryptococcal antigen (CrAg) — highly sensitive; used both for screening at CD4 < 200 and diagnosis.
▪ Lumbar puncture with measurement of opening pressure — mandatory.
▪ CSF India ink — shows encapsulated budding yeasts with a clear halo (sensitivity ~70–80%).
▪ CSF cryptococcal antigen — sensitivity > 95%; the diagnostic test of choice. [VERY HIGH-YIELD]
▪ CSF fungal culture — gold standard for confirmation and for assessing sterilisation.
▪ CSF typically shows low cell count (often < 20 cells), mildly raised protein, low-normal glucose and very high opening pressure — a paucity of inflammation reflects poor immune response.
▪ CT/MRI brain before LP if focal signs; may show cryptococcomas, dilated Virchow-Robin spaces ("soap-bubble" lesions) or hydrocephalus.
|
Phase |
Regimen |
Duration |
|
Induction |
Liposomal amphotericin B 10 mg/kg single high dose + flucytosine 100 mg/kg/day + fluconazole 1200 mg/day (WHO-preferred), or amphotericin B deoxycholate 1 mg/kg/day + flucytosine 100 mg/kg/day |
1 week (single-dose LAmB regimen) or 2 weeks (conventional) |
|
Consolidation |
Fluconazole 800 mg daily |
8 weeks |
|
Maintenance (secondary prophylaxis) |
Fluconazole 200 mg daily |
Until CD4 > 100 for ≥ 1 year with viral suppression, and ≥ 1 year of therapy completed |
▪ Management of raised intracranial pressure is as important as antifungal therapy: perform therapeutic lumbar punctures daily, removing CSF until closing pressure < 20 cm H₂O or halved, until pressure normalises. [VERY HIGH-YIELD]
▪ Do NOT use mannitol, acetazolamide or corticosteroids for raised pressure in cryptococcal meningitis — steroids increase mortality. [FAVORITE EXAM QUESTION]
▪ Amphotericin B toxicity: nephrotoxicity, hypokalaemia, hypomagnesaemia, anaemia, infusion reactions — pre-hydrate with 1 L normal saline and supplement potassium and magnesium.
▪ Flucytosine toxicity: myelosuppression and hepatotoxicity — monitor blood counts.
▪ Fluconazole: hepatotoxicity, QT prolongation; interacts with rifampicin (levels fall) and with many drugs via CYP inhibition.
|
ART Timing in Cryptococcal Meningitis [VERY HIGH-YIELD] DELAY ART by 4–6 weeks after starting antifungal therapy. Early ART (within 1–2 weeks) causes a significant increase in mortality from cryptococcal IRIS with raised intracranial pressure (COAT trial). This is one of only two OIs in which ART is deliberately delayed — the other is TB meningitis. |
▪ Cryptococcal IRIS — recurrent meningitis-like illness with sterile CSF culture, lymphadenitis or cryptococcomas; manage with repeated LPs, continued antifungals and corticosteroids only for severe IRIS (not for initial disease).
▪ Pre-emptive therapy: a person with positive serum CrAg but no meningitis (negative LP) receives fluconazole 800 mg daily × 2 weeks → 400 mg × 8 weeks → 200 mg maintenance, and ART after 2 weeks. [IMPORTANT]
▪ Relapse usually reflects inadequate induction, premature stopping of maintenance, or fluconazole resistance.
▪ Prognosis: 10-week mortality remains 25–40% even with treatment; predictors of death are altered mental status, high CSF fungal burden, low CSF white cell count and very high opening pressure.
▪ Pulmonary cryptococcosis — cough, dyspnoea, fever; nodules, mass lesions, cavities or diffuse infiltrates; often accompanies meningeal disease.
▪ Disseminated cryptococcosis — fungaemia with skin (molluscum-like umbilicated papules), bone, prostate and lymph-node involvement.
▪ Every patient with pulmonary or disseminated cryptococcosis in HIV must have a lumbar puncture to exclude meningeal involvement, which changes the regimen. [IMPORTANT]
▪ Isolated mild pulmonary disease without CNS involvement: fluconazole 400 mg daily for 6–12 months.
▪ Candida albicans predominates; non-albicans species (C. glabrata, C. krusei) emerge with repeated azole exposure.
▪ CD4 usually < 200; an important clinical marker of immunosuppression and a WHO stage 3 condition.
▪ Forms: pseudomembranous (removable white plaques leaving an erythematous base), erythematous/atrophic (palate and dorsum of tongue), hyperplastic, and angular cheilitis.
▪ Diagnosis is clinical; KOH mount or Gram stain shows budding yeasts and pseudohyphae if needed.
▪ Treatment: fluconazole 100–200 mg daily for 7–14 days (systemic therapy is preferred and more effective than topical); alternatives are clotrimazole troches, nystatin suspension, itraconazole solution.
▪ Fluconazole-refractory disease: itraconazole solution, posaconazole, voriconazole, or echinocandin/amphotericin B; consider C. glabrata/krusei.
▪ No routine primary prophylaxis — it promotes azole resistance; ART is the definitive preventive measure. [IMPORTANT]
▪ AIDS-defining; CD4 usually < 100; the commonest cause of odynophagia/dysphagia in HIV. [VERY HIGH-YIELD]
▪ Presents with retrosternal pain on swallowing; oral thrush present in most but absence does not exclude it.
▪ Diagnosis: an empirical trial of fluconazole is both diagnostic and therapeutic — response within 3–7 days confirms; endoscopy (linear white plaques and ulceration) is reserved for non-responders.
▪ Treatment: fluconazole 200 mg on day 1 then 100–200 mg daily for 14–21 days; IV fluconazole or an echinocandin if unable to swallow.
▪ Secondary prophylaxis is not routine; use ART. Consider suppressive fluconazole only for frequent severe recurrences.
▪ Histoplasma capsulatum — dimorphic fungus; soil enriched with bird and bat droppings; endemic foci in India include West Bengal, the Gangetic plain and the north-east (a recognised but under-diagnosed problem). [IMPORTANT]
▪ CD4 < 150 cells/µL for disseminated disease.
▪ Progressive disseminated histoplasmosis: fever, weight loss, hepatosplenomegaly, generalised lymphadenopathy, pancytopenia, mucosal (oral/laryngeal) ulcers, skin lesions, adrenal insufficiency, and a sepsis-like syndrome with DIC in fulminant cases.
▪ Diagnosis: Histoplasma urine/serum antigen (most sensitive in disseminated disease); bone-marrow or tissue histology with GMS/PAS showing small intracellular yeasts (2–4 µm) within macrophages; blood/marrow fungal culture; peripheral smear may show intracellular yeasts.
▪ Treatment: liposomal amphotericin B 3 mg/kg/day for 2 weeks (induction) → itraconazole 200 mg three times daily × 3 days then twice daily (consolidation) for ≥ 12 months; maintenance itraconazole until CD4 > 150 for ≥ 6 months with viral suppression.
▪ Itraconazole requires acid for absorption — avoid PPIs and antacids; take with food/cola; check drug levels; major interactions with ART (especially PIs and NNRTIs). [COMMON MCQ]
▪ Start ART within 2 weeks; monitor for IRIS.
|
A Diagnosis Not to Miss in India [VERY HIGH-YIELD] Talaromyces (Penicillium) marneffei is the third commonest AIDS-defining illness in Southeast Asia and is endemic in north-east India (Manipur, Nagaland, Mizoram, Assam), southern China, Thailand and Vietnam. Reservoir: bamboo rats and soil; incidence rises in the rainy season. |
▪ CD4 < 100 cells/µL.
▪ Clinical triad: fever, anaemia and weight loss with hepatosplenomegaly and generalised lymphadenopathy.
▪ Characteristic skin lesions: multiple umbilicated papules with central necrosis on the face, trunk and upper limbs — closely mimic molluscum contagiosum and cryptococcosis. [FAVORITE EXAM QUESTION]
▪ Diagnosis: microscopy of skin scraping, bone marrow or lymph-node aspirate showing intracellular yeast-like cells that divide by FISSION (a transverse septum), not by budding — the key distinguishing feature from Histoplasma; culture on Sabouraud agar produces a diffusible red pigment at 25 °C (mould phase) and yeast phase at 37 °C (thermal dimorphism).
▪ Treatment: liposomal amphotericin B 3–5 mg/kg/day (or amphotericin B deoxycholate 0.7–1 mg/kg/day) for 2 weeks → itraconazole 200 mg twice daily for 10 weeks → itraconazole 200 mg daily maintenance until CD4 > 100 for ≥ 6 months on ART.
▪ Start ART within 2 weeks; watch for IRIS. Untreated disseminated talaromycosis is almost uniformly fatal.
▪ Coccidioides immitis / posadasii — endemic to the southwestern United States, Mexico and parts of Central and South America; not endemic in India but reported in travellers and returning migrants.
▪ CD4 < 250 cells/µL for disseminated disease.
▪ Clinical: pneumonia, diffuse reticulonodular infiltrates, meningitis (the most feared form), skin, bone and joint disease.
▪ Diagnosis: serology (may be falsely negative in advanced HIV), culture (a laboratory biohazard — warn the laboratory), histology showing spherules containing endospores.
▪ Treatment: fluconazole 400–800 mg daily; amphotericin B for severe or refractory disease; lifelong fluconazole for coccidioidal meningitis.
▪ Aspergillus fumigatus — invasive aspergillosis is uncommon in HIV alone; risk rises with neutropenia, corticosteroid use, structural lung disease and advanced AIDS.
▪ Clinical: invasive pulmonary aspergillosis (fever, pleuritic pain, haemoptysis; halo and air-crescent signs on CT), obstructing bronchial aspergillosis (a form peculiar to AIDS), sinus and cerebral disease; also aspergilloma in old TB cavities.
▪ Diagnosis: serum/BAL galactomannan, culture and histology showing septate hyphae branching at acute (45°) angles. [COMMON MCQ]
▪ Treatment: voriconazole is first line (isavuconazole or liposomal amphotericin B as alternatives); note major interactions between voriconazole and efavirenz/ritonavir requiring dose adjustment. [IMPORTANT]
▪ Prognosis is poor; recovery depends on reversing immunosuppression.
▪ Toxoplasma gondii — obligate intracellular protozoon; definitive host is the cat; humans acquire it from oocysts in cat faeces/soil or tissue cysts in undercooked meat.
▪ Cerebral toxoplasmosis in HIV is almost always reactivation of latent infection — it therefore occurs only in those with positive Toxoplasma IgG. [VERY HIGH-YIELD]
▪ CD4 < 100 cells/µL (usually < 50). Indian seroprevalence is 20–40%, so it is a real but less frequent problem than TB.
▪ Subacute onset over days to weeks: headache, fever, confusion, focal neurological deficits (hemiparesis, aphasia, ataxia) and seizures.
▪ Altered mental status and, less commonly, features of raised intracranial pressure.
▪ Extracerebral toxoplasmosis: retinochoroiditis, pneumonitis, myocarditis, disseminated disease.
▪ Contrast MRI (preferred) or CT brain: multiple ring-enhancing lesions with surrounding oedema and mass effect, typically in the basal ganglia and at the grey-white junction. [FAVORITE EXAM QUESTION]
▪ Toxoplasma IgG — a negative IgG makes the diagnosis very unlikely and should redirect thinking to lymphoma, tuberculoma or PML.
▪ CSF PCR for T. gondii — specific but insensitive; LP is often contraindicated because of mass effect.
▪ The diagnosis is usually made by therapeutic response — clinical and radiological improvement within 10–14 days of empirical therapy confirms it.
▪ Brain biopsy — reserved for non-responders; histology shows tachyzoites with necrosis.
▪ Primary CNS lymphoma (single periventricular lesion, EBV DNA in CSF, thallium-avid), tuberculoma (very important in India), PML (non-enhancing white matter), bacterial or fungal abscess, cryptococcoma, metastasis.
▪ Induction (6 weeks minimum): Pyrimethamine 200 mg loading, then 50–75 mg daily + Sulfadiazine 1–1.5 g four times daily + Folinic acid (leucovorin) 10–25 mg daily. [VERY HIGH-YIELD]
▪ Folinic acid is mandatory to prevent pyrimethamine-induced bone-marrow suppression — folic acid must NOT be substituted, as it antagonises the drug. [FAVORITE EXAM QUESTION]
▪ Alternatives: pyrimethamine + clindamycin (for sulfa allergy); high-dose cotrimoxazole (TMP 10 mg/kg/day) — widely used in India because of cost and availability, with comparable efficacy; atovaquone-based regimens.
▪ Maintenance (secondary prophylaxis): pyrimethamine 25–50 mg + sulfadiazine 2–4 g daily + folinic acid (or cotrimoxazole 1 DS daily), until CD4 > 200 for ≥ 6 months on ART.
▪ Adjunctive measures: anticonvulsants for seizures (avoid enzyme-inducing agents where possible); dexamethasone only for significant mass effect or midline shift — steroids confound the diagnosis by shrinking lymphoma as well.
▪ Adverse effects: pyrimethamine (marrow suppression), sulfadiazine (rash, crystalluria and renal stones — maintain hydration), clindamycin (C. difficile colitis).
▪ Start ART within 2–3 weeks of beginning anti-toxoplasma therapy.
▪ Toxoplasma IRIS — paradoxical enlargement of lesions with worsening oedema; treat with steroids while continuing therapy.
▪ Primary prophylaxis: cotrimoxazole 1 DS daily for those with CD4 < 100 and positive Toxoplasma IgG (alternatives: dapsone + pyrimethamine + folinic acid, atovaquone). Stop when CD4 > 200 for ≥ 3–6 months. [IMPORTANT]
▪ Prevention advice: cook meat thoroughly, wash hands and vegetables, avoid handling cat litter (or use gloves).
▪ Prognosis: response in > 85% if treated early; relapse is common if maintenance therapy is stopped prematurely.
▪ Cryptosporidium parvum / hominis — acquired from contaminated water (chlorine-resistant oocysts), food and person-to-person contact; water-borne outbreaks are important in India.
▪ CD4 < 100–200 cells/µL for chronic disease; chronic (> 1 month) cryptosporidiosis is AIDS-defining.
▪ Clinical: profuse, watery, non-bloody, high-volume diarrhoea with cramps, malabsorption, weight loss and dehydration; may involve the biliary tree causing AIDS cholangiopathy and sclerosing cholangitis, and rarely the respiratory tract.
▪ Diagnosis: stool modified acid-fast (Kinyoun) stain showing 4–6 µm round oocysts; antigen ELISA; PCR; small-bowel biopsy. [VERY HIGH-YIELD]
▪ Treatment: there is no reliably effective specific antiparasitic drug. Effective ART with immune reconstitution is the definitive treatment. [FAVORITE EXAM QUESTION]
▪ Adjuncts: nitazoxanide 500–1000 mg twice daily (works only with some immune recovery), aggressive rehydration and electrolyte replacement, antimotility agents, nutritional support.
▪ Prevention: boil or filter drinking water (1-micron filters), avoid untreated surface water and swimming pools, hand hygiene.
▪ Cystoisospora belli — faeco-oral transmission; relatively more common in India and other tropical countries than in temperate regions. [IMPORTANT]
▪ CD4 < 200; chronic disease (> 1 month) is AIDS-defining.
▪ Clinical: watery diarrhoea, cramps, weight loss, malabsorption — often with peripheral EOSINOPHILIA, which is unusual for a protozoal infection. [COMMON MCQ]
▪ Diagnosis: stool modified acid-fast stain showing large (20–30 µm) oval oocysts containing sporoblasts; oocysts autofluoresce.
▪ Treatment: cotrimoxazole 1 DS four times daily for 10 days (or 2 DS twice daily), then secondary prophylaxis with cotrimoxazole 1 DS daily until CD4 > 200 for ≥ 6 months.
▪ Alternative in sulfa allergy: pyrimethamine + folinic acid, or ciprofloxacin.
▪ Cyclospora cayetanensis — associated with contaminated water and imported fresh produce (berries, herbs, salad leaves); seasonal (monsoon) peaks in India and Nepal.
▪ Clinical: prolonged watery diarrhoea with anorexia, fatigue, cramps and marked weight loss; relapsing course.
▪ Diagnosis: stool modified acid-fast stain showing 8–10 µm oocysts (intermediate in size between Cryptosporidium and Cystoisospora) that are autofluorescent blue-green under UV microscopy. [FAVORITE EXAM QUESTION]
▪ Treatment: cotrimoxazole 1 DS twice daily for 7–10 days, followed by secondary prophylaxis in advanced HIV until immune reconstitution.
▪ Enterocytozoon bieneusi (commonest) and Encephalitozoon intestinalis; obligate intracellular spore-forming fungi (reclassified from protozoa).
▪ CD4 usually < 100.
▪ Clinical: chronic watery diarrhoea and wasting; Encephalitozoon may disseminate to biliary tract, kidney, sinuses, eye (keratoconjunctivitis) and brain.
▪ Diagnosis: stool modified trichrome (Weber) stain or Calcofluor white; small (1–3 µm) spores; electron microscopy or PCR for species identification; duodenal biopsy.
▪ Treatment: albendazole 400 mg twice daily for 21 days is effective for Encephalitozoon but NOT for E. bieneusi; fumagillin is the only agent active against E. bieneusi; ART with immune reconstitution is the mainstay. [IMPORTANT]
▪ Leishmania donovani transmitted by the sandfly (Phlebotomus argentipes); endemic in Bihar, Jharkhand, West Bengal and eastern Uttar Pradesh — HIV-VL coinfection is a recognised Indian problem. [VERY HIGH-YIELD]
▪ CD4 usually < 200; HIV increases the risk of VL 100–1000 fold and VL accelerates HIV progression.
▪ Clinical: prolonged fever, massive splenomegaly, hepatomegaly, pancytopenia, wasting, hypergammaglobulinaemia; atypical presentations with gastrointestinal, pulmonary and cutaneous involvement are characteristic in HIV.
▪ Diagnosis: rK39 rapid antigen test is less sensitive in HIV; splenic or bone-marrow aspirate demonstrating LD (Leishman-Donovan) bodies (amastigotes) is the gold standard; PCR has high sensitivity. [IMPORTANT]
▪ Treatment: liposomal amphotericin B (total dose 30–40 mg/kg) — preferred in India, often combined with miltefosine; higher relapse rates than in HIV-negative patients.
▪ Secondary prophylaxis (e.g. monthly liposomal amphotericin B or oral miltefosine) is recommended until CD4 > 200–350; relapse rates remain high.
▪ Also note post-kala-azar dermal leishmaniasis (PKDL) which may be atypical and severe in HIV.
▪ Strongyloides stercoralis — soil-transmitted nematode with an autoinfective cycle enabling decades-long persistence; endemic in rural India.
▪ Hyperinfection syndrome and disseminated strongyloidiasis are precipitated chiefly by corticosteroids and HTLV-1 coinfection, and are less strictly CD4-dependent than other OIs — but occur in advanced HIV. [VERY HIGH-YIELD]
▪ Clinical: abdominal pain, diarrhoea, malabsorption, cough and wheeze (Löffler-like), larva currens (pathognomonic serpiginous migratory rash); hyperinfection presents with ileus, respiratory failure, and Gram-negative bacteraemia/meningitis from gut organisms carried by migrating larvae.
▪ Diagnosis: stool microscopy (repeated; agar plate culture increases yield), duodenal aspirate, sputum larvae in hyperinfection, serology, eosinophilia (may be absent in hyperinfection or with steroids).
▪ Treatment: ivermectin 200 µg/kg/day for 2 days (uncomplicated) or daily until larvae cleared for ≥ 2 weeks (hyperinfection); albendazole is a less effective alternative.
▪ Key clinical rule: screen for and treat strongyloidiasis before giving corticosteroids to any patient from an endemic area. [IMPORTANT]
▪ Human herpesvirus 5; seroprevalence in India exceeds 90%, so disease is virtually always reactivation.
▪ CD4 < 50 cells/µL — the classic threshold. [VERY HIGH-YIELD]
▪ CMV viraemia or a positive PCR alone does not equal disease — end-organ involvement must be demonstrated.
▪ The commonest CMV end-organ disease (~80–85%); the leading infectious cause of blindness in AIDS.
▪ Symptoms: floaters, blurred vision, painless progressive visual field loss ("curtain"), photopsia; painless and initially unilateral.
▪ Fundoscopy: perivascular yellow-white areas of retinal necrosis with haemorrhage — the "pizza-pie" or "cottage cheese and ketchup" appearance, spreading along vascular arcades. [FAVORITE EXAM QUESTION]
▪ Diagnosis is clinical, by an experienced ophthalmologist on dilated fundoscopy; aqueous/vitreous PCR in atypical cases.
▪ Treatment: valganciclovir 900 mg twice daily for 14–21 days (induction) → 900 mg once daily (maintenance); IV ganciclovir if unable to take orals; intravitreal ganciclovir or foscarnet for immediately sight-threatening zone-1 (posterior pole) lesions.
▪ Alternatives: foscarnet (nephrotoxicity, electrolyte disturbance, seizures), cidofovir (nephrotoxicity — give with probenecid and hydration).
▪ Ganciclovir toxicity: neutropenia, thrombocytopenia and anaemia — avoid combining with zidovudine. [IMPORTANT]
▪ Stop maintenance when CD4 > 100 for ≥ 3–6 months with viral suppression and lesions inactive, after ophthalmology review.
▪ Delay ART by ~2 weeks; watch for immune recovery uveitis (vitritis, macular oedema, cataract) as a form of IRIS.
▪ Complications: retinal detachment, macular involvement, permanent visual loss.
▪ Fever, bloody diarrhoea, abdominal pain, weight loss; may perforate or bleed massively.
▪ Colonoscopy shows subepithelial haemorrhage, erosions and deep well-demarcated ulcers; biopsy shows large cells with "owl-eye" intranuclear inclusions and positive immunohistochemistry. [VERY HIGH-YIELD]
▪ Treatment: IV ganciclovir or oral valganciclovir for 21–42 days, or until symptoms resolve; maintenance is often not required if ART is effective.
▪ Odynophagia with a single large, deep, well-circumscribed ulcer in the distal oesophagus; diagnosed on endoscopic biopsy from the ulcer base.
▪ Treatment: ganciclovir/valganciclovir for 21–42 days.
▪ CMV pneumonitis — diffuse interstitial infiltrates; requires histological confirmation, since CMV in BAL is common without disease.
▪ CMV neurological disease — encephalitis (ventriculoencephalitis with periventricular enhancement), polyradiculomyelitis (ascending flaccid paraparesis with urinary retention and neutrophilic CSF — a classic examination scenario). [COMMON MCQ]
▪ CMV adrenalitis — an important cause of adrenal insufficiency in AIDS.
▪ Chronic mucocutaneous HSV ulceration lasting > 1 month is AIDS-defining; also visceral disease (oesophagitis, bronchitis, pneumonitis, hepatitis).
▪ Presentation: extensive, painful, persistent orolabial, genital or perianal ulceration; often atypical and hypertrophic in advanced disease.
▪ Disseminated HSV — visceral involvement with hepatitis, pneumonitis and encephalitis.
▪ Diagnosis: clinical; PCR of a swab is the test of choice; Tzanck smear (multinucleated giant cells) is insensitive; viral culture; biopsy for atypical lesions.
▪ Treatment: aciclovir 400 mg five times daily (or valaciclovir 1 g BD, famciclovir 500 mg BD) for 5–14 days; IV aciclovir 5–10 mg/kg 8-hourly for severe, visceral or CNS disease.
▪ Aciclovir-resistant HSV (thymidine kinase-deficient) occurs with prolonged suppressive therapy in advanced HIV → treat with foscarnet or cidofovir. [IMPORTANT]
▪ Chronic suppressive therapy (aciclovir 400 mg BD or valaciclovir 500 mg BD) for frequent recurrences; also reduces genital HIV shedding.
▪ Herpes zoster in a young adult should prompt HIV testing; it is a WHO stage 2 condition and may occur at relatively preserved CD4 counts. [VERY HIGH-YIELD]
▪ Features in HIV: multidermatomal, recurrent, prolonged, haemorrhagic or necrotic lesions, severe post-herpetic neuralgia.
▪ Disseminated zoster — > 20 lesions outside the primary dermatome, or visceral involvement (pneumonitis, hepatitis, encephalitis); a medical emergency requiring IV therapy.
▪ Ophthalmic zoster (V1) — risk of keratitis, uveitis and acute retinal necrosis / progressive outer retinal necrosis, which can cause rapid bilateral blindness.
▪ VZV vasculopathy — stroke weeks after zoster, particularly with ophthalmic involvement.
▪ Treatment: localised zoster — aciclovir 800 mg five times daily or valaciclovir 1 g TDS for 7–10 days; disseminated, ophthalmic or CNS disease — IV aciclovir 10 mg/kg 8-hourly.
▪ Primary varicella (chickenpox) in an adult with HIV can be severe — treat with IV aciclovir; VZIG within 96 hours for susceptible exposed patients.
▪ Recombinant zoster vaccine (Shingrix) is safe (non-live) and recommended; the live attenuated zoster vaccine is contraindicated at CD4 < 200. [IMPORTANT]
▪ JC polyomavirus — reactivation of latent infection (seroprevalence > 50%) causing lytic infection of oligodendrocytes and consequent demyelination.
▪ CD4 < 100 cells/µL (usually < 50); AIDS-defining.
▪ Clinical: progressive focal neurological deficits over weeks — hemiparesis, visual field defects/cortical blindness, ataxia, aphasia, cognitive decline — characteristically WITHOUT fever, headache or features of raised intracranial pressure. [FAVORITE EXAM QUESTION]
▪ MRI: asymmetrical, non-enhancing, no mass effect white-matter lesions, hyperintense on T2/FLAIR, involving subcortical U-fibres; typically parieto-occipital.
▪ Diagnosis: JC virus PCR in CSF with compatible MRI; brain biopsy (bizarre astrocytes, enlarged oligodendrocyte nuclei with inclusions) if PCR is negative but suspicion is high.
▪ Treatment: there is NO specific antiviral therapy. ART with immune reconstitution is the only effective treatment — it has changed 1-year survival from ~10% to ~50%. [VERY HIGH-YIELD]
▪ PML-IRIS — paradoxical worsening with new contrast enhancement and oedema after ART; treat with corticosteroids while continuing ART; do not stop ART.
▪ Prognosis: deficits acquired are usually permanent; ART must be started immediately on diagnosis.
▪ Oral hairy leukoplakia — non-scrapable corrugated white plaques on the lateral tongue; benign and diagnostic of immunosuppression; responds to ART (aciclovir if symptomatic).
▪ Primary CNS lymphoma — nearly 100% EBV-associated; EBV DNA in CSF is a useful diagnostic marker.
▪ Systemic non-Hodgkin lymphoma — Burkitt (EBV in ~30–40%), diffuse large B-cell/immunoblastic (EBV in ~80%).
▪ Hodgkin lymphoma — nearly always EBV-associated in HIV.
▪ Lymphoid interstitial pneumonitis (LIP) in children — EBV-driven; presents with chronic cough, clubbing and reticulonodular infiltrates; responds to ART ± steroids. [IMPORTANT]
▪ Smooth-muscle tumours (leiomyosarcoma) in children with HIV are EBV-associated.
▪ Norovirus, rotavirus, astrovirus, adenovirus and picobirnavirus may cause prolonged or chronic diarrhoea in advanced HIV, unlike the self-limiting illness in immunocompetent hosts.
▪ Diagnosis: stool antigen tests, PCR panels, electron microscopy.
▪ Treatment is supportive — rehydration and nutrition — with ART as the definitive measure; nitazoxanide has been used with variable success for norovirus.
▪ Durable virological suppression — HIV RNA below the limit of detection, maintained lifelong.
▪ Immune recovery — restoration and preservation of CD4 count and function.
▪ Prevention of opportunistic infections and of AIDS-defining malignancies.
▪ Reduction in morbidity — both AIDS and non-AIDS events.
▪ Reduction in mortality — near-normal life expectancy when started early.
▪ Prevention of transmission — sexual (U = U), vertical and, indirectly, at population level.
▪ Improvement in quality of life — physical, psychological and social.
▪ Prevention of drug resistance — through full suppression and sustained adherence. [IMPORTANT]
|
Treat All [VERY HIGH-YIELD] ART is indicated for every person with confirmed HIV infection, at any CD4 count, at any WHO stage, at any age, including pregnant and breastfeeding women. Rapid ART initiation (within 7 days of diagnosis) and same-day ART are recommended for those who are ready — this improves linkage, retention and survival. |
▪ Conditions requiring stabilisation before ART: the patient must first be assessed and treated for opportunistic infection, and specifically screened for TB and cryptococcal disease.
|
Clinical situation |
When to start ART |
|
Acute HIV infection |
Immediately — same day if possible |
|
Pregnancy |
Immediately, at any gestation and any CD4 [VERY HIGH-YIELD] |
|
Tuberculosis (non-meningeal), CD4 < 50 |
Within 2 weeks of ATT |
|
Tuberculosis (non-meningeal), CD4 ≥ 50 |
Within 8 weeks of ATT |
|
Tuberculous meningitis |
Delay 4–8 weeks — early ART increases mortality |
|
Cryptococcal meningitis |
Delay 4–6 weeks after starting antifungals [FAVORITE EXAM QUESTION] |
|
Toxoplasmosis |
Within 2–3 weeks |
|
Pneumocystis pneumonia |
Within 2 weeks |
|
CMV retinitis |
Delay ~2 weeks (risk of immune recovery uveitis) |
|
HBV coinfection |
Immediately, using an HBV-active regimen (TDF + 3TC/FTC) |
|
Critically ill patients |
Stabilise first; individualise; do not delay beyond 2 weeks unless CNS OI |
|
Class |
Mechanism |
Examples |
|
NRTIs (nucleoside RT inhibitors) |
Chain terminators after intracellular phosphorylation |
Zidovudine, lamivudine, emtricitabine, abacavir, stavudine, didanosine |
|
NtRTIs (nucleotide RT inhibitors) |
As above but already monophosphorylated |
Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) |
|
NNRTIs |
Non-competitive allosteric binding to reverse transcriptase |
Efavirenz, nevirapine, rilpivirine, etravirine, doravirine |
|
Protease inhibitors |
Block cleavage of Gag-Pol polyprotein → immature non-infectious virions |
Lopinavir/r, atazanavir/r, darunavir/r, ritonavir (booster) |
|
INSTIs |
Block strand transfer by integrase |
Dolutegravir, bictegravir, raltegravir, elvitegravir, cabotegravir |
|
CCR5 antagonists |
Block CCR5 coreceptor (R5-tropic virus only) |
Maraviroc |
|
Fusion inhibitors |
Bind gp41, preventing membrane fusion |
Enfuvirtide (subcutaneous) |
|
Attachment inhibitors |
Bind gp120, preventing CD4 attachment |
Fostemsavir |
|
Post-attachment inhibitors |
Anti-CD4 monoclonal blocking conformational change |
Ibalizumab (IV) |
|
Capsid inhibitors |
Disrupt capsid function at multiple steps |
Lenacapavir (6-monthly injection) |
|
Pharmacokinetic boosters |
CYP3A4 inhibition to raise partner drug levels |
Ritonavir, cobicistat |
|
Drug |
Dose & notes |
Key adverse effects |
|
Tenofovir DF (TDF) |
300 mg OD; renal dose adjustment required; HBV-active |
Nephrotoxicity (Fanconi syndrome), reduced bone mineral density [VERY HIGH-YIELD] |
|
Tenofovir alafenamide (TAF) |
25 mg OD; better renal and bone safety; HBV-active |
Weight gain and dyslipidaemia; avoid with rifampicin |
|
Lamivudine (3TC) |
300 mg OD; renal adjustment; HBV-active |
Very well tolerated; HBV flare on withdrawal |
|
Emtricitabine (FTC) |
200 mg OD; HBV-active |
Well tolerated; skin hyperpigmentation |
|
Zidovudine (AZT) |
300 mg BD; take with or without food |
Macrocytic anaemia, neutropenia, myopathy, lipoatrophy, nausea, headache |
|
Abacavir (ABC) |
600 mg OD; HLA-B*57:01 must be negative |
Hypersensitivity reaction (fever, rash, GI, respiratory) — never rechallenge; possible CVD risk |
|
Stavudine (d4T) |
Withdrawn from national programmes |
Lipoatrophy, peripheral neuropathy, lactic acidosis, pancreatitis |
|
Didanosine (ddI) |
Withdrawn |
Pancreatitis, neuropathy, non-cirrhotic portal hypertension |
|
Drug |
Dose & notes |
Key adverse effects |
|
Efavirenz (EFV) |
400–600 mg at bedtime, on an empty stomach; compatible with rifampicin |
CNS effects: vivid dreams, dizziness, insomnia, mood change, rarely psychosis and suicidality; rash; false-positive cannabis screen; gynaecomastia [VERY HIGH-YIELD] |
|
Nevirapine (NVP) |
200 mg OD × 14 days lead-in then 200 mg BD |
Severe hepatotoxicity and rash/SJS — risk highest in women with CD4 > 250 and men with CD4 > 400; do not use as PEP [FAVORITE EXAM QUESTION] |
|
Rilpivirine (RPV) |
25 mg OD with a full meal; avoid if VL > 100,000 or CD4 < 200 |
Contraindicated with PPIs; QT prolongation; depression |
|
Etravirine (ETR) |
200 mg BD with food; second-generation, active against some NNRTI-resistant virus |
Rash, hypersensitivity |
|
Doravirine (DOR) |
100 mg OD; higher barrier than older NNRTIs |
Well tolerated; avoid with rifampicin |
|
Drug |
Dose & notes |
Key adverse effects |
|
Lopinavir/ritonavir (LPV/r) |
400/100 mg BD; heat-stable tablets |
Diarrhoea, nausea, dyslipidaemia, insulin resistance, PR/QT prolongation |
|
Atazanavir/ritonavir (ATV/r) |
300/100 mg OD with food; needs gastric acid |
Unconjugated hyperbilirubinaemia with jaundice (benign), nephrolithiasis; avoid PPIs [COMMON MCQ] |
|
Darunavir/ritonavir (DRV/r) |
800/100 mg OD (naive) or 600/100 mg BD (experienced) |
Highest genetic barrier among PIs; rash (sulfonamide moiety), dyslipidaemia |
|
Ritonavir (booster) |
100 mg; used only as a pharmacokinetic enhancer |
GI upset; potent CYP3A4 inhibitor — a source of very many interactions |
|
Drug |
Dose & notes |
Key adverse effects |
|
|
Dolutegravir (DTG) |
50 mg OD; 50 mg BD with rifampicin; high genetic barrier; the backbone of Indian first-line ART |
Weight gain, insomnia, headache, mood change; small creatinine rise (blocks tubular secretion, not true renal injury); hyperglycaemia [VERY HIGH-YIELD] |
|
|
Bictegravir (BIC) |
50 mg OD, only as BIC/FTC/TAF single tablet |
Similar to DTG; avoid with rifampicin |
|
|
Raltegravir (RAL) |
400 mg BD (or 1200 mg OD); safe in pregnancy and with rifampicin (800 mg BD) |
Rash, rare rhabdomyolysis; lower genetic barrier |
|
|
Cabotegravir (CAB) |
Oral lead-in then long-acting IM every 2 months with rilpivirine |
Injection-site reactions; not for use with rifampicin |
|
|
Maraviroc (MVC) |
150–600 mg BD depending on interacting drugs; only for R5-tropic virus — tropism test first |
Hepatotoxicity, postural hypotension |
|
|
Enfuvirtide (T-20) |
90 mg SC twice daily |
Injection-site reactions in almost all patients; increased bacterial pneumonia |
|
|
Fostemsavir / Ibalizumab / Lenacapavir |
Salvage therapy for multidrug-resistant HIV |
Nausea; infusion/injection reactions; injection-site nodules |
|
|
For each drug remember the checklist: Mechanism · Dose · Formulation · Food requirement · Adverse effects · Contraindications · Renal adjustment · Hepatic adjustment · Pregnancy safety · Drug interactions · Resistance pattern. ▪ Renal adjustment needed: all NRTIs except abacavir; TDF is the key one. [COMMON MCQ] ▪ Hepatic adjustment/caution: nevirapine, PIs, maraviroc; avoid nevirapine in Child-Pugh B/C. ▪ Food: efavirenz on an empty stomach; rilpivirine and atazanavir with food; dolutegravir with or without food but 2 hours before or 6 hours after antacids/calcium/iron. [VERY HIGH-YIELD] |
|||
|
Indian National Programme (NACO) First-Line Regimen [VERY HIGH-YIELD] TLD = Tenofovir 300 mg + Lamivudine 300 mg + Dolutegravir 50 mg — one fixed-dose tablet once daily, provided free at all ART centres. Advantages: high potency, high genetic barrier, low pill burden, few interactions, low cost, rapid viral suppression, and safety in pregnancy. |
▪ Preferred global regimens: TDF/TAF + 3TC/FTC + dolutegravir; or bictegravir/FTC/TAF as a single tablet.
▪ Alternative regimens: TDF + 3TC + efavirenz 400 mg (TLE); abacavir + 3TC + dolutegravir (if TDF contraindicated by renal disease — requires HLA-B*57:01 negative); zidovudine + 3TC + DTG (second-line NRTI backbone in India when TDF fails or is contraindicated).
▪ Two-drug regimens in selected virologically suppressed patients: dolutegravir + lamivudine (not if HBV coinfected, VL > 500,000 or resistance unknown); dolutegravir + rilpivirine; long-acting cabotegravir + rilpivirine injections.
▪ Paediatric regimens: dolutegravir-based (dispersible tablets, DTG 10 mg) with abacavir + lamivudine; lopinavir/r-based regimens where DTG is unavailable.
|
Comorbidity |
Preferred approach |
|
Hepatitis B |
Must include TDF (or TAF) + 3TC/FTC — two HBV-active drugs; never use 3TC alone (resistance); never stop abruptly (flare) [VERY HIGH-YIELD] |
|
Tuberculosis (on rifampicin) |
Dolutegravir 50 mg BD, or efavirenz at standard dose; avoid PIs, bictegravir, TAF, rilpivirine |
|
Renal disease (eGFR < 50) |
Avoid TDF → use abacavir (with HLA-B*57:01 testing) or TAF (down to eGFR 30); dose-adjust 3TC/FTC/AZT |
|
Liver disease |
Avoid nevirapine; caution with PIs; dolutegravir and raltegravir are relatively safe |
|
Pregnancy |
TDF + 3TC + dolutegravir is preferred and safe; avoid the older concern regarding neural tube defects (now shown not to be significant) |
|
Cardiovascular disease |
Avoid abacavir and boosted PIs where possible; aggressive risk-factor control |
|
Osteoporosis |
Avoid TDF → TAF or abacavir; vitamin D and calcium |
|
Psychiatric illness |
Avoid efavirenz; use caution with dolutegravir if insomnia/mood symptoms; PIs and raltegravir are alternatives |
|
Obesity / metabolic syndrome |
Note weight gain with INSTIs and TAF; counsel on diet and exercise |
|
Major drug interactions (e.g. anticonvulsants) |
Choose raltegravir or dolutegravir with dose adjustment; involve a pharmacist |
|
Adverse effect |
Culprit drug(s) |
Management |
|
Nephrotoxicity / Fanconi syndrome |
TDF |
Monitor creatinine, eGFR, urine protein, phosphate; switch to TAF or abacavir |
|
Reduced bone density |
TDF, PIs |
Vitamin D, calcium, switch to TAF/abacavir |
|
Anaemia and neutropenia |
Zidovudine |
Monitor Hb; switch to TDF |
|
Hypersensitivity reaction |
Abacavir |
Stop permanently — never rechallenge (fatal on re-exposure); HLA-B*57:01 screening prevents it [VERY HIGH-YIELD] |
|
Neuropsychiatric toxicity |
Efavirenz (dizziness, dreams, psychosis), dolutegravir (insomnia) |
Dose at bedtime; usually settles in 2–4 weeks; switch if persistent |
|
Hepatotoxicity |
Nevirapine (first 12 weeks), PIs, efavirenz |
Stop nevirapine permanently for symptomatic hepatitis or rash with hepatitis |
|
Rash and SJS/TEN |
Nevirapine, efavirenz, abacavir, cotrimoxazole |
Stop drug; supportive care; never rechallenge after severe reaction |
|
Dyslipidaemia |
PIs (especially LPV/r), efavirenz |
Diet, statins (use atorvastatin/rosuvastatin at low dose; avoid simvastatin and lovastatin with PIs) [FAVORITE EXAM QUESTION] |
|
Hyperbilirubinaemia (unconjugated) |
Atazanavir, indinavir |
Benign; reassure; switch only for cosmetic distress |
|
Insulin resistance / diabetes |
PIs, INSTI-related weight gain |
Lifestyle, metformin, screen annually |
|
Lipodystrophy |
Stavudine, zidovudine (atrophy); PIs (accumulation) |
Switch off thymidine analogues; lipoatrophy is only partly reversible |
|
Lactic acidosis / hepatic steatosis |
Stavudine, didanosine, zidovudine |
Stop NRTIs immediately; supportive care; potentially fatal |
|
Mitochondrial toxicity |
Thymidine analogues |
Neuropathy, myopathy, pancreatitis, steatosis — switch drug |
|
Weight gain |
Dolutegravir, bictegravir, TAF |
Diet, exercise; more marked in women and Black patients |
|
Interacting agent |
Effect and management |
|
Rifampicin |
Potent inducer: double dolutegravir to 50 mg BD; efavirenz unchanged; PIs, bictegravir, TAF and rilpivirine are contraindicated [VERY HIGH-YIELD] |
|
Rifabutin |
Weaker inducer — substitute for rifampicin when a PI is essential (rifabutin 150 mg daily with boosted PI) |
|
Anticonvulsants (phenytoin, carbamazepine, phenobarbitone) |
Reduce ART levels — use valproate, levetiracetam or lamotrigine instead |
|
Antacids, calcium and iron (polyvalent cations) |
Chelate dolutegravir and other INSTIs → give DTG 2 hours before or 6 hours after, or with food [FAVORITE EXAM QUESTION] |
|
Proton-pump inhibitors |
Contraindicated with rilpivirine and atazanavir (need gastric acid for absorption) |
|
Azole antifungals |
Bidirectional CYP interactions with PIs and NNRTIs; rifampicin lowers azole levels; monitor and adjust |
|
Macrolides (clarithromycin) |
Levels rise with PIs; QT prolongation risk — azithromycin is safer |
|
Methadone / buprenorphine |
Efavirenz and PIs reduce methadone levels → withdrawal; adjust dose |
|
Oral contraceptives |
Efavirenz and PIs reduce efficacy → use DMPA, IUCD or dual protection [IMPORTANT] |
|
Direct-acting antivirals for HCV |
Multiple interactions — check regimen compatibility before starting |
|
Statins |
Avoid simvastatin and lovastatin with PIs (rhabdomyolysis); use low-dose atorvastatin, rosuvastatin or pitavastatin |
|
Corticosteroids (inhaled/intranasal fluticasone) |
Ritonavir/cobicistat cause accumulation → iatrogenic Cushing syndrome and adrenal suppression; use beclometasone |
|
Herbal medicines (St John's wort) |
Potent inducer — contraindicated with all ART; ayurvedic and other preparations may be hepatotoxic |
▪ Importance: > 95% adherence is traditionally quoted for NNRTI/PI regimens; INSTI-based regimens are more forgiving, but adherence remains the single most important determinant of outcome. [VERY HIGH-YIELD]
▪ Barriers: stigma and non-disclosure, depression and substance use, pill burden and side effects, cost of transport, migration, food insecurity, forgetfulness, misinformation and alternative medicine, and treatment fatigue.
▪ Assessment: self-report (over-estimates), pill counts, pharmacy refill records, viral load (the objective gold standard), and treatment-supporter reports.
▪ Counselling: individual, group and peer-based; Enhanced Adherence Counselling (EAC) is mandatory before declaring failure in the Indian programme.
▪ Pill burden and fixed-dose combinations — single-tablet regimens such as TLD greatly improve adherence.
▪ Missed doses: take as soon as remembered unless the next dose is due; never double the dose.
▪ Treatment interruptions: structured interruptions are harmful (SMART trial) and must be avoided; unplanned interruptions risk resistance and HBV flare. [IMPORTANT]
▪ Differentiated service delivery: multi-month dispensing (3–6 months), community ART refill groups, fast-track pick-up, and Link ART Centres reduce clinic burden and improve retention.
▪ Transmitted (primary) resistance — the patient is infected with an already-resistant virus; baseline genotype is advised where prevalence > 10%.
▪ Acquired (secondary) resistance — develops under drug pressure with incomplete suppression, almost always due to poor adherence.
▪ Genotypic testing — sequencing of pol to detect resistance mutations; the standard test; must be done while the patient is still on the failing regimen (or within 4 weeks of stopping). [IMPORTANT]
▪ Phenotypic testing — measures actual drug susceptibility; expensive, used for complex salvage.
▪ Archived resistance — mutations stored in the latent reservoir that are not detectable in plasma but re-emerge when a drug is reused; treatment history is therefore as important as the genotype.
|
Mutation |
Significance |
|
M184V |
Lamivudine/emtricitabine resistance; increases susceptibility to tenofovir/zidovudine and reduces viral fitness — often retained deliberately [FAVORITE EXAM QUESTION] |
|
K65R |
Tenofovir, abacavir resistance |
|
TAMs (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E) |
Thymidine analogue mutations — zidovudine/stavudine resistance, cross-resistance to other NRTIs |
|
K103N |
High-level efavirenz and nevirapine resistance; no effect on etravirine |
|
Y181C |
NNRTI resistance including partial etravirine |
|
Q148H/R/K + G140S |
Integrase resistance — the principal pathway to dolutegravir failure |
|
N155H, Y143R |
Raltegravir and elvitegravir resistance |
|
I50L |
Atazanavir-specific resistance |
|
I50V, I84V, V82A |
Protease inhibitor resistance |
▪ Cross-resistance is extensive within the NNRTI class (K103N covers efavirenz and nevirapine) and substantial within NRTIs; INSTIs show partial cross-resistance (raltegravir/elvitegravir failure may retain dolutegravir activity, but Q148 pathway mutations reduce it).
|
Approach to Confirmed Virological Failure Confirm viraemia — VL > 1000 copies/mL on two occasions ≥ 3 months apart ↓ Adherence assessment — enhanced adherence counselling × 3 sessions; treatment supporter; address depression and substance use ↓ Drug-interaction and dosing assessment — rifampicin, antacids, anticonvulsants, herbal products, food requirements, malabsorption ↓ Resistance testing (genotype) while still on therapy, where available; otherwise use programme algorithms ↓ Construct a new regimen with at least 2 (preferably 3) fully active drugs — never add a single agent to a failing regimen ↓ Refer to SACEP / Centre of Excellence for second- and third-line approval in the Indian programme |
▪ First-line failure (TLD): switch to a boosted PI-based second line — e.g. zidovudine + lamivudine + darunavir/ritonavir (or lopinavir/r); retaining 3TC despite M184V is deliberate.
▪ Second-line failure: third-line therapy guided by genotype — darunavir/ritonavir + dolutegravir (often twice daily) ± etravirine ± an optimised NRTI backbone.
▪ Salvage therapy for multidrug-resistant virus: fostemsavir, ibalizumab, lenacapavir, maraviroc (if R5-tropic), enfuvirtide; the aim remains full suppression, or if impossible, preservation of CD4 and clinical stability.
▪ High genetic-barrier drugs — dolutegravir, bictegravir and darunavir/ritonavir — should anchor any salvage regimen. [VERY HIGH-YIELD]
▪ Reasons to switch: toxicity, simplification/reduced pill burden, drug interactions (e.g. starting rifampicin), pregnancy, comorbid disease (renal, bone, cardiovascular), food or dosing inconvenience, and cost.
▪ Golden rule for a switch in a suppressed patient: the new regimen must be at least as potent, and the full treatment and resistance history must be reviewed — a switch that unmasks archived resistance causes rebound. [IMPORTANT]
▪ Check viral load 4–8 weeks after any switch.
|
HBV Flare After Withdrawal of HBV-Active Drugs [FAVORITE EXAM QUESTION] Stopping tenofovir, lamivudine or emtricitabine in a patient with chronic hepatitis B can precipitate a severe hepatitis flare with hepatic decompensation and death. → Always check HBsAg before switching or stopping ART. If HBV-positive, the regimen must retain tenofovir + lamivudine/emtricitabine, whatever else is changed. |
IRIS is a paradoxical clinical deterioration occurring after initiation of ART, resulting from the restoration of pathogen-specific immune responses that produce an exaggerated inflammatory reaction against an existing (treated or subclinical) infection or antigen, despite virological and immunological improvement.
|
Mechanism of IRIS Advanced HIV with low CD4 → high burden of pathogen antigen and profound immune anergy ↓ ART started → rapid fall in viral load and rapid restoration of CD4 cells and pathogen-specific responses ↓ Dysregulated restoration: massive release of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6), with slower recovery of regulatory T cells ↓ Exaggerated inflammatory response against residual antigen at sites of infection ↓ Clinical deterioration — despite falling viral load and rising CD4 |
▪ Paradoxical IRIS — worsening of a known, already-diagnosed and treated opportunistic infection after starting ART.
▪ Unmasking IRIS — a previously subclinical/undiagnosed infection becomes clinically apparent, with unusually inflammatory features, after starting ART. [VERY HIGH-YIELD]
▪ Low baseline CD4 (< 50–100 cells/µL) — the strongest risk factor.
▪ High baseline viral load and a rapid fall in viral load after ART.
▪ High pathogen antigen burden — disseminated TB, cryptococcal meningitis.
▪ Short interval between starting OI treatment and starting ART.
▪ ART-naive patients starting therapy for the first time.
▪ Timing: usually within 2–12 weeks of starting ART, most commonly in the first 4–8 weeks; occasionally later. [IMPORTANT]
|
IRIS syndrome |
Clinical features |
|
Tuberculosis IRIS |
The commonest form in India. Recurrent fever, enlarging lymph nodes (may suppurate), worsening infiltrates, new effusions, expanding CNS tuberculomas, ARDS in severe cases |
|
Cryptococcal IRIS |
Recurrent meningitis symptoms with raised intracranial pressure but STERILE CSF culture; lymphadenitis; cryptococcomas; potentially fatal [VERY HIGH-YIELD] |
|
MAC IRIS |
Focal suppurative lymphadenitis (cervical, abdominal), fever, abscess formation |
|
CMV IRIS |
Immune recovery uveitis and vitritis in previously treated retinitis; macular oedema, cataract, visual loss |
|
Zoster IRIS |
Herpes zoster, often multidermatomal, in the first months of ART — the commonest mild IRIS event |
|
PML-IRIS |
Paradoxical worsening of deficits with new contrast enhancement and oedema on MRI (previously non-enhancing lesions) |
|
HBV and HCV flares |
Rise in transaminases from restored immune attack on infected hepatocytes; may cause decompensation |
|
Kaposi sarcoma IRIS |
Rapid enlargement, oedema and new lesions; pulmonary KS may deteriorate acutely |
|
Other |
Leprosy reactions, sarcoidosis, Graves disease (late, at months to years), autoimmune disease, eosinophilic folliculitis, molluscum |
|
Working Diagnostic Criteria for IRIS [IMPORTANT] 1. Confirmed HIV infection with recent initiation, re-initiation or switch of ART. 2. Evidence of treatment response: fall in HIV RNA of ≥ 1 log₁₀ (and/or a rise in CD4). 3. Clinical deterioration consistent with an inflammatory process, temporally related to ART. 4. Exclusion of alternative explanations — treatment failure of the OI, drug resistance, poor adherence, a new opportunistic infection, drug toxicity or hypersensitivity, and malignancy. IRIS is therefore a diagnosis of exclusion. |
▪ Progression of the opportunistic infection — because of inadequate or ineffective OI therapy (e.g. drug-resistant TB, wrong diagnosis).
▪ ART treatment failure — but in early IRIS the viral load is falling, not rising.
▪ A new opportunistic infection — always culture and image before attributing deterioration to IRIS.
▪ Drug toxicity or hypersensitivity reaction — abacavir hypersensitivity, nevirapine or cotrimoxazole reaction, drug-induced liver injury.
▪ Malignancy — lymphoma may masquerade as an inflammatory relapse.
▪ Poor adherence or malabsorption of OI drugs.
▪ Continue ART in almost all cases — stopping it risks rebound viraemia, resistance and further OI. [VERY HIGH-YIELD]
▪ Continue and optimise OI treatment — ensure adequate dosing and susceptibility.
▪ Mild disease: symptomatic treatment and NSAIDs.
▪ Moderate-to-severe disease: corticosteroids — prednisolone 1–1.5 mg/kg/day (or dexamethasone) tapered over 2–6 weeks; dramatically effective in TB-IRIS. [IMPORTANT]
▪ Drainage of collections — suppurative lymph nodes, abscesses, empyema, pericardial effusion.
▪ Repeated therapeutic lumbar punctures for cryptococcal IRIS with raised intracranial pressure.
▪ Rare indications for interrupting ART: life-threatening IRIS unresponsive to steroids — particularly CNS IRIS with impending herniation; even then, interruption is brief and reluctant.
▪ Prevention: screen for and treat opportunistic infections before starting ART; observe the recommended delays in cryptococcal and TB meningitis; prophylactic prednisolone 40 mg daily for 4 weeks reduces paradoxical TB-IRIS in high-risk patients (CD4 < 100 starting ART within 30 days of ATT).
▪ Most IRIS is self-limiting over weeks to months and does not indicate ART failure.
▪ Mortality is low overall (< 5%) but substantially higher in CNS IRIS, particularly cryptococcal and tuberculous meningitis IRIS.
▪ IRIS should never be a reason to withhold ART — the long-term benefit of ART far outweighs the risk. [IMPORTANT]
|
Framework — Analyse Every HIV Malignancy By [IMPORTANT] Etiological virus · Risk factors · Pathogenesis · Clinical features · Diagnosis · Staging · Treatment · ART considerations · Drug interactions · Prognosis · Screening · Prevention. Most HIV-associated cancers are virus-driven: HHV-8 (Kaposi sarcoma, primary effusion lymphoma, Castleman disease), EBV (CNS and systemic lymphoma, Hodgkin lymphoma), HPV (cervical, anal, oropharyngeal, vulvar and vaginal cancer), HBV/HCV (hepatocellular carcinoma). |
▪ Etiological virus: Human herpesvirus 8 (HHV-8 / KSHV). [VERY HIGH-YIELD]
▪ Risk factors: low CD4 (usually < 200), MSM (higher HHV-8 seroprevalence), male sex, absence of ART. Uncommon in India relative to Africa, reflecting low HHV-8 seroprevalence.
▪ Pathogenesis: HHV-8 infects endothelial cells; viral proteins (vGPCR, vIL-6, LANA) drive angiogenesis and spindle-cell proliferation; HIV Tat acts as a co-factor.
▪ Clinical features: violaceous/brown macules, plaques and nodules following skin cleavage lines, typically on the lower limbs, face, trunk and hard palate; painless but may ulcerate; lymphoedema is characteristic.
▪ Visceral disease: gastrointestinal (bleeding, obstruction) and pulmonary KS (nodular infiltrates, effusion, haemoptysis — poor prognosis).
▪ Diagnosis: biopsy showing spindle cells forming slit-like vascular spaces with extravasated red cells and haemosiderin; LANA-1 (HHV-8) immunohistochemistry is confirmatory. [FAVORITE EXAM QUESTION]
▪ Staging: ACTG TIS system — Tumour extent, Immune status (CD4), Systemic illness; good risk = T0 or I0 or S0.
▪ Treatment: ART alone produces regression in many patients with limited cutaneous disease; add liposomal doxorubicin (or paclitaxel) for extensive, visceral, symptomatic or rapidly progressive disease; local therapy (intralesional vinblastine, radiotherapy) for cosmetic lesions.
▪ ART considerations: ART is essential; watch for KS-IRIS with acute enlargement and oedema — in pulmonary KS this can be life-threatening, so chemotherapy is given with ART.
▪ Prognosis: excellent with ART for limited disease; pulmonary involvement carries the worst outcome.
▪ Etiological virus: EBV in most immunoblastic/DLBCL cases and ~30–40% of Burkitt lymphoma; chronic B-cell stimulation and c-MYC translocation.
▪ Subtypes: Burkitt lymphoma (may occur at high CD4), diffuse large B-cell/immunoblastic lymphoma (low CD4), plasmablastic lymphoma (characteristically oral cavity/jaw, CD20-negative, highly aggressive — strongly HIV-associated). [VERY HIGH-YIELD]
▪ Clinical features: rapidly enlarging nodal or extranodal masses (GI tract, bone marrow, liver, CNS), B symptoms, very high LDH; extranodal and advanced-stage disease is the norm in HIV.
▪ Diagnosis: excision biopsy with immunohistochemistry; bone-marrow biopsy; CSF examination in all (high risk of leptomeningeal spread); CT/PET-CT for staging (Ann Arbor).
▪ Treatment: standard-intensity chemotherapy — R-CHOP or DA-EPOCH-R for DLBCL; intensive regimens (CODOX-M/IVAC or DA-EPOCH-R) for Burkitt; CNS prophylaxis with intrathecal methotrexate/cytarabine.
▪ Rituximab caution: avoid or use carefully if CD4 < 50 because of increased infectious deaths.
▪ ART considerations: continue ART throughout chemotherapy; avoid zidovudine (additive myelosuppression); watch PI–chemotherapy interactions (ritonavir raises vincristine and cyclophosphamide toxicity) — INSTI-based regimens are preferred during chemotherapy. [IMPORTANT]
▪ Supportive care: G-CSF, cotrimoxazole prophylaxis, antifungal and antiviral prophylaxis, tumour lysis prophylaxis in Burkitt.
▪ Prognosis: now approaches that of HIV-negative lymphoma when ART and full-dose chemotherapy are given.
▪ Etiological virus: EBV in essentially 100% of cases. [VERY HIGH-YIELD]
▪ CD4 usually < 50 cells/µL; incidence has fallen dramatically with ART.
▪ Clinical features: subacute focal deficits, personality and cognitive change, seizures, raised intracranial pressure; constitutional symptoms and fever are typically absent (unlike toxoplasmosis).
▪ Imaging: usually a single (or few) periventricular lesion with ring or homogeneous enhancement, may cross the corpus callosum; less oedema per lesion size than toxoplasmosis.
▪ Diagnosis: EBV DNA PCR in CSF (high specificity), thallium-201 SPECT or FDG-PET showing avid uptake (toxoplasmosis is not avid), and stereotactic brain biopsy for definitive diagnosis. [FAVORITE EXAM QUESTION]
▪ Distinguish from cerebral toxoplasmosis: single vs multiple lesions, negative Toxoplasma IgG, no response to a 2-week trial of anti-toxoplasma therapy.
▪ Treatment: high-dose methotrexate-based chemotherapy with ART; whole-brain radiotherapy for those unfit for chemotherapy; corticosteroids relieve oedema but must be withheld until biopsy if possible (they lyse lymphoma cells and obscure histology). [IMPORTANT]
▪ Prognosis: historically dismal (median survival 2–3 months); markedly improved with ART plus methotrexate.
▪ Etiological virus: high-risk HPV (types 16 and 18 predominantly); HIV impairs HPV clearance.
▪ Risk factors: low CD4, persistent high-risk HPV, smoking, multiple partners, other STIs.
▪ Women with HIV have a ~6-fold higher risk of cervical cancer, with faster progression from CIN to invasive disease and higher recurrence after treatment. [VERY HIGH-YIELD]
▪ Clinical features: post-coital or intermenstrual bleeding, foul discharge, pelvic pain; advanced disease with hydronephrosis and fistulae.
▪ Diagnosis: speculum examination, Pap cytology/VIA/HPV DNA, colposcopy with biopsy; imaging for staging.
▪ Staging: FIGO staging.
▪ Treatment: as for HIV-negative women — surgery for early disease, concurrent chemoradiation (cisplatin-based) for locally advanced disease; ART throughout.
▪ Screening and prevention: cervical screening at HIV diagnosis and annually (or per national protocol) — not the 3–5 yearly interval used for HIV-negative women; HPV vaccination for eligible girls and young women; condoms; early ART. [IMPORTANT]
▪ These now account for a greater share of cancer deaths in PLHIV than AIDS-defining cancers, reflecting longer survival, chronic inflammation, smoking and viral coinfections. [VERY HIGH-YIELD]
|
Malignancy |
Driver / risk factor |
Key points |
|
Hodgkin lymphoma |
EBV (~100% in HIV) |
5–15-fold higher risk; mixed cellularity and lymphocyte-depleted subtypes predominate; advanced stage with marrow involvement; ABVD with ART gives good outcomes |
|
Anal carcinoma |
HPV 16/18 |
Highest risk in MSM; screen with digital anorectal examination ± anal cytology and high-resolution anoscopy |
|
Hepatocellular carcinoma |
HBV, HCV, alcohol, fatty liver |
6-monthly ultrasound ± AFP surveillance in cirrhosis and in HBV [IMPORTANT] |
|
Lung cancer |
Smoking + HIV-related inflammation |
2–3-fold higher risk; presents younger and at more advanced stage; smoking cessation is the single most valuable intervention |
|
Oropharyngeal cancer |
HPV, tobacco, alcohol, areca nut/gutkha (India) |
Oral examination at every visit; tobacco cessation |
|
Vulvar and vaginal cancer |
HPV |
Inspect the vulva and vagina at cervical screening |
|
Testicular cancer (seminoma) |
Unclear; modest excess risk |
Any testicular mass needs ultrasound and urology referral |
|
Skin cancer |
UV exposure, HPV, immunosuppression |
Basal and squamous cell carcinoma; more aggressive behaviour |
|
Others |
— |
Head and neck, gastric, colorectal, renal, multiple myeloma, leiomyosarcoma (children, EBV) |
▪ Multicentric Castleman disease (MCD) — HHV-8-driven polyclonal lymphoproliferation; relapsing-remitting fever, generalised lymphadenopathy, splenomegaly, cytopenias, hypoalbuminaemia and very high CRP and HHV-8 viral load; diagnosis by lymph-node biopsy (plasma-cell variant); treated with rituximab (± liposomal doxorubicin) plus ART; may co-exist with Kaposi sarcoma. [VERY HIGH-YIELD]
▪ KSHV inflammatory cytokine syndrome (KICS) — severe systemic inflammation with high HHV-8 viral load and cytokine storm but without the histological features of Castleman disease; high mortality.
▪ Primary effusion lymphoma (PEL) — a rare, highly aggressive HHV-8-positive (usually EBV co-infected) lymphoma presenting as lymphomatous effusions (pleural, pericardial, peritoneal) WITHOUT a tumour mass; diagnosed on effusion cytology and immunophenotype; poor prognosis. [FAVORITE EXAM QUESTION]
|
The Changing Face of HIV Care [VERY HIGH-YIELD] With effective ART, PLHIV now die predominantly of non-AIDS causes — cardiovascular disease, non-AIDS cancers, chronic liver and kidney disease. This reflects chronic immune activation and persistent inflammation even under viral suppression, compounded by traditional risk factors, drug toxicity and ageing. Long-term HIV care is therefore chronic-disease care with the same rigour as diabetes or hypertension management. |
▪ Premature cardiovascular disease — 1.5–2-fold higher risk of myocardial infarction and stroke; contributors are inflammation, dyslipidaemia (PIs), smoking, abacavir (debated) and traditional factors. Assess ASCVD/Framingham risk annually and use statins liberally, checking interactions. [IMPORTANT]
▪ Hypertension — check BP at every visit; standard management applies; avoid interactions (calcium channel blockers with ritonavir).
▪ Diabetes mellitus — screen with fasting glucose/HbA1c annually; higher risk with PIs, INSTI-associated weight gain and HCV.
▪ Dyslipidaemia — annual fasting lipids; diet, exercise, statin (atorvastatin, rosuvastatin, pitavastatin); switch away from PIs where possible.
▪ Chronic kidney disease — annual eGFR and urine protein; avoid nephrotoxins; TDF → TAF/abacavir if declining function; control BP and glucose.
▪ Chronic liver disease — treat HBV and HCV, limit alcohol, manage fatty liver, screen for fibrosis (FIB-4, elastography) and for HCC in cirrhosis.
▪ Chronic lung disease — COPD, bronchiectasis, pulmonary hypertension; spirometry when symptomatic; smoking cessation.
▪ Osteopenia and osteoporosis — 3-fold higher; assess FRAX from age 40–50, vitamin D and calcium, DEXA where indicated, switch from TDF if fracture risk is high.
▪ Non-AIDS cancers — implement age-appropriate and HIV-specific screening (cervical, anal, hepatocellular, lung in smokers, breast and colorectal per national guidance).
▪ Ageing with HIV — more than half of PLHIV in high-income settings are now over 50; multimorbidity is the norm.
▪ Frailty and sarcopenia — occur a decade earlier than in HIV-negative peers; assess gait speed, grip strength and weight loss; manage with resistance exercise and nutrition.
▪ Neurocognitive impairment — screen periodically (IHDS/MoCA); optimise ART, treat depression, control vascular risk.
▪ Polypharmacy — review all medicines at every visit for interactions and deprescribing opportunities; involve a pharmacist. [IMPORTANT]
▪ Persistent inflammation — raised IL-6, D-dimer and sCD14 predict mortality; there is no proven anti-inflammatory intervention beyond ART, statins and risk-factor control.
▪ Depression — screen at least annually; treat with SSRIs (checking PI interactions) and psychological therapy; untreated depression is a leading cause of non-adherence.
▪ Substance use — brief interventions, opioid-substitution therapy, alcohol reduction, tobacco cessation support.
▪ Sexual health — periodic STI screening, condom provision, partner testing, PrEP for partners, and management of sexual dysfunction.
▪ Reproductive health and fertility — preconception counselling, safe conception with U = U or PrEP, contraception advice, assisted reproduction where needed.
▪ Menopause — occurs earlier in women with HIV; manage vasomotor symptoms, bone and cardiovascular risk.
▪ Nutrition — balanced high-protein diet, food safety, micronutrients; nutritional assessment at every visit; link to social-protection schemes.
▪ Exercise — combined aerobic and resistance training improves metabolic profile, muscle mass, mood and cardiovascular risk.
▪ Smoking cessation — the single most impactful intervention for long-term survival in virally suppressed PLHIV. [VERY HIGH-YIELD]
▪ Dental care — six-monthly review; periodontal disease is common and often neglected.
▪ Mental-health care — integrated psychological services, peer counsellors and positive-people networks.
▪ Social and occupational rehabilitation — vocational training, legal aid, protection from workplace discrimination under the HIV/AIDS Act 2017, and linkage to government welfare schemes.
▪ Palliative care — symptom control (pain, nausea, breathlessness), advance care planning and end-of-life care for those with refractory disease or advanced malignancy.
▪ Preconception counselling — achieve full viral suppression before conception; optimise regimen; folic acid; screen and treat STIs; discuss U = U and safer conception.
▪ ART in pregnancy — start immediately at any gestation and any CD4; TDF + 3TC + dolutegravir (TLD) is the preferred regimen and is safe in pregnancy. [VERY HIGH-YIELD]
▪ Historic concern regarding dolutegravir and neural tube defects (Tsepamo study) has not been confirmed on longer follow-up; DTG is now recommended throughout pregnancy, including the first trimester. [COMMON MCQ]
▪ Avoid in pregnancy: efavirenz is acceptable but not preferred; avoid stavudine + didanosine (lactic acidosis); avoid nevirapine initiation if CD4 > 250.
▪ Maternal monitoring — CD4, viral load, Hb, LFT, RFT, glucose; screen for TB, syphilis, HBV, HCV; monitor adherence closely.
▪ Viral-load monitoring — at baseline, at ART initiation, and importantly at 34–36 weeks to plan delivery.
▪ Mode of delivery: if viral load < 1000 copies/mL, vaginal delivery is safe; elective caesarean section at 38 weeks is offered if viral load > 1000 copies/mL or unknown. [VERY HIGH-YIELD]
▪ Intrapartum care: avoid artificial rupture of membranes, invasive fetal scalp monitoring, fetal scalp blood sampling, routine episiotomy and instrumental delivery; minimise duration of ruptured membranes; use active management of the third stage (avoid ergometrine with PIs).
▪ Continue maternal ART lifelong after delivery.
▪ Infant prophylaxis: nevirapine (± zidovudine) syrup daily for 6 weeks for low-risk infants; extended prophylaxis (12 weeks, dual drug) for high-risk infants (mother diagnosed late, not on ART, or not virally suppressed). [IMPORTANT]
▪ Infant feeding — NACO/WHO recommendation for India: EXCLUSIVE BREASTFEEDING for 6 months, then complementary feeding with continued breastfeeding up to 12 months, provided the mother is on ART with viral suppression. Mixed feeding must be avoided — it carries the highest transmission risk. [VERY HIGH-YIELD]
▪ Replacement feeding is advised only when it is AFASS — Acceptable, Feasible, Affordable, Sustainable and Safe.
▪ Early infant diagnosis — HIV DNA PCR at 6 weeks, repeat as per schedule, 6 weeks after cessation of breastfeeding, and final antibody test at 18 months.
▪ Cotrimoxazole prophylaxis for all HIV-exposed infants from 6 weeks until infection is excluded.
▪ Contraception postnatally — condoms plus a reliable method; note interactions with hormonal contraceptives.
▪ Routes of acquisition: vertical transmission (the great majority), transfusion, sexual abuse, and in adolescents, sexual acquisition and injecting drug use.
▪ Clinical features: recurrent bacterial infections, persistent oral thrush, chronic diarrhoea, parotid enlargement, lymphoid interstitial pneumonitis, hepatosplenomegaly, chronic otitis media.
▪ Growth failure — failure to thrive and stunting are cardinal features; monitor weight and height at every visit.
▪ Developmental delay and HIV encephalopathy — regression of milestones, microcephaly, spastic diplegia.
▪ Paediatric staging — WHO clinical staging with paediatric-specific items; CD4 percentage is used under 5 years. [IMPORTANT]
▪ Infant diagnosis — virological testing (DNA/RNA PCR) as detailed in section 10.6.
▪ Paediatric ART: start in all children immediately after diagnosis, especially urgent in infants (untreated infant mortality reaches 50% by 2 years). Preferred: ABC + 3TC + dolutegravir (dispersible formulations); lopinavir/r-based regimens as alternatives.
▪ Disclosure — a staged, age-appropriate process, usually completed by 10–12 years; essential for adherence and mental health.
▪ Adherence in adolescents is notoriously poor — related to disclosure, stigma, peer pressure, mental health and treatment fatigue; adolescents have the worst viral suppression rates of any age group. [VERY HIGH-YIELD]
▪ Transition to adult care — planned, gradual handover with joint clinics; abrupt transition causes loss to follow-up.
▪ Adolescent-friendly services, sexual and reproductive health education, and mental-health support are essential. Under Indian law (POCSO Act), any sexual activity involving a person under 18 years is reportable — clinicians must be aware of mandatory reporting obligations while protecting the young person's welfare. [IMPORTANT]
▪ Diagnosis — four-symptom screen at every visit; CBNAAT/Truenat as the first test; urine LF-LAM if CD4 < 200 or seriously ill; remember atypical and normal radiographs.
▪ Drug interactions — rifampicin requires dolutegravir 50 mg twice daily; PIs must be replaced or rifabutin substituted; check every co-prescribed drug.
▪ ART timing — within 2 weeks if CD4 < 50; within 8 weeks otherwise; delay 4–8 weeks in TB meningitis.
▪ TB preventive therapy — 6H (or 3HP/3HR) for all PLHIV once active TB is excluded, regardless of CD4 or ART status.
▪ TB-IRIS — anticipate, treat with steroids, and continue both therapies.
▪ Drug-resistant TB — all-oral bedaquiline-containing regimens; beware overlapping toxicities (QT prolongation, myelosuppression, neuropathy) and the need for ECG monitoring.
▪ Programme integration: every TB patient must be tested for HIV, and every PLHIV screened for TB — the NACO–NTEP single-window cross-referral system with Nikshay reporting. [VERY HIGH-YIELD]
▪ HBV-active ART is mandatory — the regimen must contain tenofovir + lamivudine/emtricitabine; lamivudine alone rapidly selects resistance. [VERY HIGH-YIELD]
▪ HBV flare — occurs on withdrawal of HBV-active drugs or as immune-reconstitution hepatitis; can cause fatal decompensation. Always check HBsAg before any regimen change.
▪ HBV vaccination for all non-immune patients; higher-dose or double-dose schedules improve response in HIV; check anti-HBs after the series.
▪ HCV treatment — direct-acting antivirals (sofosbuvir + daclatasvir/velpatasvir, glecaprevir/pibrentasvir) achieve > 95% sustained virological response regardless of HIV status; India has generic access at low cost. [IMPORTANT]
▪ Drug interactions with DAAs — avoid efavirenz with certain DAAs; check the regimen combination before prescribing; ledipasvir/sofosbuvir raises tenofovir levels.
▪ Hepatocellular carcinoma surveillance — 6-monthly ultrasound (± AFP) in cirrhosis and in chronic HBV, continuing even after HCV cure.
▪ Assess fibrosis in all coinfected patients (FIB-4, APRI, transient elastography) and manage portal hypertension.
▪ ART selection: avoid TDF if eGFR < 50 mL/min; use abacavir (HLA-B*57:01 negative) or TAF (usable down to eGFR 30).
▪ Dose adjustment: lamivudine, emtricitabine and zidovudine require renal dose reduction; abacavir, dolutegravir, efavirenz, nevirapine and PIs do not. [COMMON MCQ]
▪ Nephrotoxicity monitoring: creatinine, eGFR, urine protein-creatinine ratio and serum phosphate; distinguish the benign creatinine rise of dolutegravir and cotrimoxazole (blockade of tubular creatinine secretion, no true GFR change) from real injury.
▪ Dialysis and transplantation are appropriate for PLHIV; HIV is no longer a contraindication to renal transplantation when the virus is suppressed. [IMPORTANT]
▪ ART selection: dolutegravir, raltegravir and abacavir are relatively safe; avoid nevirapine in Child-Pugh B/C; use PIs with caution.
▪ Hepatotoxicity monitoring: ALT at baseline, at 2, 4, 8 and 12 weeks with nevirapine, and whenever symptoms occur.
▪ Dose adjustment in hepatic impairment for PIs, maraviroc and some NNRTIs; consult specific product information.
▪ Avoid alcohol, hepatotoxic herbal remedies and unnecessary paracetamol overdosing; vaccinate against hepatitis A and B.
▪ Frailty — screen with gait speed and grip strength; encourage resistance exercise.
▪ Comorbidities — hypertension, diabetes, CKD, osteoporosis, cardiovascular disease occur earlier and more frequently.
▪ Polypharmacy — high interaction burden; use INSTI-based regimens with fewer interactions; deprescribe where possible.
▪ Neurocognitive disease — distinguish HAND from Alzheimer and vascular dementia; screen periodically.
▪ CD4 recovery is slower in older patients — another argument for early diagnosis and treatment. [IMPORTANT]
▪ Needle and syringe programmes (NSP) — provision of sterile injecting equipment; a core NACO targeted-intervention component.
▪ Opioid substitution therapy (OST) — buprenorphine (commonly used in India) or methadone; improves retention, adherence and reduces injecting risk; note that efavirenz and PIs reduce methadone levels and may precipitate withdrawal. [VERY HIGH-YIELD]
▪ Hepatitis B vaccination and HCV testing and treatment for all.
▪ Adherence — directly observed or supported therapy, co-located ART and OST services, peer navigators.
▪ Drug interactions — ART with methadone, buprenorphine, benzodiazepines (avoid midazolam with PIs).
▪ Screen for and treat injection-site infections, endocarditis, tetanus, overdose risk (naloxone provision) and mental illness.
▪ Hormone–ART interactions — efavirenz and ritonavir alter oestrogen and antiandrogen levels; INSTI-based regimens (dolutegravir, bictegravir) have minimal interactions and are preferred. [IMPORTANT]
▪ Never advise stopping gender-affirming hormones to accommodate ART — this is a major cause of ART refusal; adjust the ART instead.
▪ Screening — for STIs at all relevant anatomical sites, cervical/anal cytology as anatomically appropriate, mental health, and hormone monitoring.
▪ Stigma-sensitive care — use the person's chosen name and pronouns, ensure privacy, train staff, and provide gender-affirming, non-judgemental services; transgender persons have among the highest HIV prevalence and lowest service uptake in India.
▪ Continuity of care — the single greatest challenge; interruption on arrest, release, transfer or migration causes resistance. Provide transfer-out/transfer-in documentation and multi-month dispensing. [VERY HIGH-YIELD]
▪ Confidentiality — particularly difficult in custodial settings; ensure private consultation and discreet drug dispensing.
▪ Screening — voluntary HIV, TB, HBV, HCV and STI screening at entry to prison and among migrant workers.
▪ Prevention — condoms, needle-syringe and OST programmes in prisons where permitted, safe tattooing advice, PEP availability.
▪ Adherence support — peer educators, treatment supporters, and linkage to ART centres near the destination for migrants; NACO facilitates inter-state transfer of ART records.
▪ Effective ART is the most powerful preventive measure — immune reconstitution prevents virtually all opportunistic infections. [VERY HIGH-YIELD]
▪ Primary prophylaxis — drug given to prevent a first episode of an infection in a susceptible person.
▪ Secondary prophylaxis (maintenance therapy) — drug continued after treatment to prevent relapse.
▪ Starting criteria — determined by CD4 count, WHO stage or a specific serological/antigen marker.
▪ Stopping criteria — sustained CD4 recovery above the threshold for 3–6 months (12 months for cryptococcosis) with viral suppression.
▪ Restarting prophylaxis — mandatory if CD4 falls below the threshold again. [IMPORTANT]
▪ Food safety — thoroughly cooked meat and eggs (toxoplasma, salmonella, listeria); avoid unpasteurised milk and soft cheese (listeria, brucella); wash fruits and vegetables (cyclospora, cryptosporidium).
▪ Water safety — boiled or filtered (1-micron) drinking water; avoid untreated surface water and ice from unknown sources (cryptosporidium, cyclospora).
▪ Environmental precautions — avoid soil and dust exposure without protection (histoplasma, cryptococcus, nocardia, talaromyces); avoid caves and bird roosts; avoid demolition and excavation sites.
▪ Animal exposure — avoid handling cat litter or use gloves and wash hands (toxoplasma); avoid stray/young cats and cat scratches (bartonella); avoid contact with reptiles and young farm animals (salmonella, cryptosporidium).
▪ Travel advice — food and water precautions, malaria chemoprophylaxis, travel vaccines (avoiding live vaccines at low CD4), and awareness of regionally endemic infections (histoplasmosis, talaromycosis, leishmaniasis).
▪ Sexual and injecting risk reduction — condoms, safer injecting, avoiding faeco-oral exposure.
|
Prophylaxis |
Indication (start) |
Regimen |
Stop when |
|
|
Cotrimoxazole (universal) |
CD4 < 200, WHO stage 3 or 4, or oral candidiasis; in India often given to all at diagnosis until CD4 known |
1 DS (960 mg) daily |
CD4 > 200 for ≥ 3–6 months on ART [VERY HIGH-YIELD] |
|
|
Pneumocystis prophylaxis |
CD4 < 200 or CD4% < 14 |
Cotrimoxazole; alternatives dapsone, atovaquone, aerosolised pentamidine |
CD4 > 200 for ≥ 3–6 months |
|
|
Toxoplasma prophylaxis |
CD4 < 100 AND Toxoplasma IgG positive |
Cotrimoxazole 1 DS daily (or dapsone + pyrimethamine + folinic acid) |
CD4 > 200 for ≥ 3–6 months |
|
|
TB preventive therapy |
All PLHIV once active TB is excluded, any CD4 |
6H (isoniazid 300 mg + pyridoxine × 6 months); or 3HP, 3HR |
On completion of the course |
|
|
MAC prophylaxis |
CD4 < 50 — no longer routinely recommended where ART is available |
Azithromycin 1200 mg weekly (historical) |
CD4 > 100 for ≥ 3 months |
|
|
Cryptococcal antigen screening |
All with CD4 < 200 |
Serum/plasma CrAg; if positive, LP to exclude meningitis |
Not applicable — a screening step |
|
|
Pre-emptive antifungal therapy |
CrAg positive, meningitis excluded |
Fluconazole 800 mg × 2 weeks → 400 mg × 8 weeks → 200 mg maintenance |
CD4 > 100 for ≥ 1 year with suppression |
|
|
Malaria prevention |
Endemic areas / travel |
Insecticide-treated nets, chemoprophylaxis; cotrimoxazole gives partial protection |
As per exposure |
|
|
Varicella post-exposure prophylaxis |
Non-immune PLHIV exposed to chickenpox/zoster |
VZIG within 96 hours, or aciclovir prophylaxis |
After the incubation period |
|
|
Cotrimoxazole — The Workhorse of Indian HIV Care [FAVORITE EXAM QUESTION] A single daily double-strength tablet simultaneously prevents: Pneumocystis pneumonia · Toxoplasmosis · Cystoisosporiasis · Nocardiosis · Many bacterial infections (pneumococcus, salmonella) · Partial protection against malaria. It reduces all-cause mortality in advanced HIV — which is why NACO recommends it broadly and early. |
||||
|
The Golden Rule of Vaccination in HIV [VERY HIGH-YIELD] Inactivated, subunit, toxoid, recombinant and mRNA vaccines are SAFE at any CD4 count. LIVE vaccines are CONTRAINDICATED when CD4 < 200 cells/µL (or CD4% < 15 in children). Whenever possible, vaccinate after immune reconstitution on ART — responses are much better with a higher CD4 count and suppressed viral load. |
|||
|
Vaccine |
Type |
Recommendation in HIV |
|
|
Influenza |
Inactivated |
Annually, all PLHIV; the live intranasal vaccine is contraindicated |
|
|
COVID-19 |
mRNA / protein subunit / inactivated |
Recommended for all, with boosters as per national schedule |
|
|
Pneumococcal |
Conjugate (PCV) + polysaccharide (PPSV23) |
PCV first, then PPSV23 ≥ 8 weeks later; revaccinate PPSV23 after 5 years [IMPORTANT] |
|
|
Hepatitis A |
Inactivated |
If non-immune, especially MSM, PWID and those with chronic liver disease |
|
|
Hepatitis B |
Recombinant |
All non-immune PLHIV; use double dose or 4-dose schedule; check anti-HBs after the series |
|
|
HPV |
Recombinant |
All PLHIV up to age 26 (consider up to 45), both sexes; 3-dose schedule in HIV |
|
|
Tetanus-diphtheria-pertussis (Tdap/Td) |
Toxoid |
Standard schedule; Td booster every 10 years |
|
|
Meningococcal (ACWY) |
Conjugate |
2-dose primary series with boosters every 5 years |
|
|
Recombinant zoster vaccine (Shingrix) |
Non-live recombinant |
Safe and recommended for adults ≥ 18–50 years with HIV |
|
|
MMR |
LIVE |
Only if CD4 ≥ 200 and non-immune; contraindicated below 200 |
|
|
Varicella |
LIVE |
Only if CD4 ≥ 200 and non-immune; contraindicated below 200 |
|
|
Yellow fever |
LIVE |
Only if CD4 ≥ 200 and travel is unavoidable |
|
|
Oral polio, BCG, oral typhoid (Ty21a), live zoster, intranasal influenza |
LIVE |
CONTRAINDICATED in symptomatic HIV / CD4 < 200. BCG is contraindicated in HIV-infected infants [FAVORITE EXAM QUESTION] |
|
|
The Three Pillars of Combination Prevention [VERY HIGH-YIELD] 1. Behavioural interventions — information, education and communication; condom promotion; partner reduction; delayed sexual debut; risk-reduction counselling; peer education. 2. Biomedical interventions — ART/TasP, PrEP, PEP, male circumcision, STI treatment, blood safety, PPTCT, needle-syringe programmes and OST. 3. Structural interventions — laws against discrimination, gender equity, poverty alleviation, education, empowerment of key populations, and reduction of stigma. No single intervention is sufficient — prevention works only in combination. |
▪ Condoms — male and female condoms are the mainstay; correct and consistent use reduces transmission by 80–95%; free distribution and social marketing under NACP.
▪ Lubricants — water- or silicone-based only; oil-based lubricants (petroleum jelly, oils) degrade latex and increase breakage. [COMMON MCQ]
▪ STI diagnosis and treatment — syndromic management under the NACP "Suraksha Clinic" designated STI/RTI services; treating genital ulcer disease markedly reduces HIV transmission.
▪ Voluntary medical male circumcision — ~60% reduction in female-to-male transmission; a major intervention in Africa, of limited applicability in India.
▪ Partner reduction and avoidance of concurrent partnerships.
▪ Sexual counselling — risk assessment, negotiation skills, disclosure support.
▪ Treatment as prevention (TasP) — early ART for all; HPTN 052 demonstrated a 96% reduction in linked transmissions. [VERY HIGH-YIELD]
▪ U = U — a person with sustained viral load < 200 copies/mL does not transmit HIV sexually; this message improves adherence, reduces stigma and enables safe conception.
▪ Definition: antiretroviral drugs taken by an HIV-negative person to prevent acquisition.
▪ Substantial ongoing risk: serodiscordant partner not virally suppressed, MSM and transgender persons with unprotected anal sex, sex workers, PWID, recent STI, repeated use of PEP, and anyone who requests it after risk assessment. [IMPORTANT]
▪ Oral daily PrEP: TDF/FTC (300/200 mg) once daily — the standard; TAF/FTC as an alternative (not for vaginal exposure).
▪ Event-driven ("2-1-1") PrEP: 2 tablets 2–24 hours before sex, 1 tablet at 24 hours, 1 tablet at 48 hours — effective only for MSM/anal exposure; NOT validated for vaginal exposure. [FAVORITE EXAM QUESTION]
▪ Long-acting injectable PrEP: cabotegravir IM every 2 months; lenacapavir subcutaneously every 6 months — superior adherence and efficacy; the dapivirine vaginal ring is a further option for women.
▪ Baseline HIV test is mandatory — giving PrEP to an undiagnosed HIV-positive person amounts to dual-drug therapy and selects resistance (especially M184V). [VERY HIGH-YIELD]
▪ Renal evaluation — creatinine and eGFR; TDF/FTC PrEP requires eGFR ≥ 60.
▪ HBV evaluation (HBsAg) — TDF/FTC also treats HBV; stopping PrEP in an HBV carrier may cause a flare.
▪ Pregnancy testing and contraception counselling; PrEP is safe in pregnancy and breastfeeding.
▪ STI and syphilis screening at baseline and 3-monthly.
▪ Follow-up: HIV test every 3 months, renal function 6-monthly, adherence and risk-reduction counselling at every visit.
▪ Adherence is the determinant of efficacy — > 90% protection with high adherence, negligible protection with poor adherence.
▪ Breakthrough infection — rare; suspect with seroconversion symptoms; stop PrEP, confirm diagnosis and start full ART; test for resistance.
▪ PrEP protects against HIV only — it does not prevent other STIs or pregnancy.
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PEP — Step-by-Step [VERY HIGH-YIELD] Exposure (occupational or non-occupational) ↓ First aid — wash the wound with soap and running water; irrigate mucosa/eyes with water or saline. Do NOT squeeze, scrub, or apply bleach/antiseptic caustics ↓ Exposure-risk assessment — type of fluid, type of exposure, depth, device, source status and viral load ↓ Baseline testing of the exposed person — HIV, HBsAg, anti-HBs, anti-HCV, LFT, RFT, pregnancy test; source testing with consent ↓ START PEP AS SOON AS POSSIBLE — ideally within 2 hours; the outer limit is 72 hours ↓ Regimen: TDF + 3TC (or FTC) + Dolutegravir, once daily for 28 days (three-drug PEP is now standard for all exposures) ↓ Counselling — condom use, no blood/organ/semen donation, avoid pregnancy and breastfeeding decisions for 3 months, adherence and side-effect support ↓ Follow-up HIV testing at 6 weeks, 3 months and 6 months (6 months especially after HCV co-exposure) |
▪ Occupational PEP — healthcare workers, laboratory staff, sanitation workers; must be available 24 × 7 in every hospital with a designated nodal officer. [IMPORTANT]
▪ Non-occupational PEP — after sexual assault, condom failure, consensual high-risk sex, or needle sharing.
▪ Timing — efficacy falls sharply with delay; PEP is not recommended beyond 72 hours.
▪ Duration — 28 days, complete course; adherence is often poor because of nausea and anxiety — provide antiemetics and support.
▪ Avoid nevirapine for PEP — risk of severe hepatotoxicity and rash in HIV-negative persons. [COMMON MCQ]
▪ Pregnancy — PEP is safe and should not be withheld; use TDF + 3TC + DTG.
▪ Sexual assault — PEP plus emergency contraception, STI prophylaxis (azithromycin + ceftriaxone + metronidazole), hepatitis B vaccination ± HBIG, tetanus prophylaxis, psychological support and forensic/medico-legal documentation; for a survivor under 18 years, mandatory reporting under the POCSO Act applies. [VERY HIGH-YIELD]
▪ Transition from PEP to PrEP — if ongoing risk continues, start PrEP immediately after completing PEP (after a negative HIV test), with no gap.
▪ Standard (universal) precautions — treat every patient's blood and body fluids as potentially infectious; this, not HIV testing of patients, is the basis of protection. [VERY HIGH-YIELD]
▪ Safe injection practices — single-use auto-disable syringes, never recap needles (or use single-handed scoop technique), never bend or break needles.
▪ Sharps disposal — puncture-proof containers at the point of use; NEVER overfill.
▪ Blood screening — mandatory testing of all donated blood for HIV, HBsAg, anti-HCV, syphilis and malaria; voluntary non-remunerated donation; NAT where available.
▪ Sterilisation and disinfection — autoclaving of instruments; HIV is readily inactivated by heat, 1% sodium hypochlorite, 70% alcohol, glutaraldehyde and hydrogen peroxide.
▪ Personal protective equipment — gloves, gown, mask and eye protection appropriate to the procedure.
▪ Exposure reporting — a clear, blame-free reporting system with a designated nodal officer and 24-hour access to a PEP starter pack.
▪ Biomedical waste management — as per the Bio-Medical Waste Management Rules; colour-coded segregation.
▪ Needle and syringe programmes — free sterile equipment; reduces HIV incidence dramatically without increasing drug use.
▪ Opioid substitution therapy — buprenorphine or methadone; a core NACO targeted-intervention component in the north-east and Punjab.
▪ Safe-injection education — never share needles, syringes, cookers, filters or water; clean skin; naloxone for overdose.
▪ Hepatitis B vaccination and HCV testing and treatment for all PWID.
▪ Linkage to ART, TB screening, mental-health services and de-addiction programmes; peer-led outreach is the most effective delivery model. [IMPORTANT]
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The PPTCT Cascade in India [VERY HIGH-YIELD] Maternal HIV testing at first ANC visit (and retest in third trimester in high-burden settings); test the partner ↓ Maternal ART — start immediately, any gestation, any CD4; TDF + 3TC + DTG; lifelong therapy ↓ Viral-load suppression — check at 34–36 weeks to plan delivery ↓ Obstetric management — vaginal delivery if VL < 1000; elective LSCS at 38 weeks if VL > 1000 or unknown; avoid invasive procedures and prolonged rupture of membranes ↓ Neonatal prophylaxis — nevirapine syrup daily for 6 weeks (extended dual prophylaxis 12 weeks for high-risk infants) ↓ Infant feeding — exclusive breastfeeding for 6 months; never mixed feeding ↓ Cotrimoxazole from 6 weeks + early infant diagnosis by DNA PCR at 6 weeks, then per schedule, and final antibody test at 18 months |
▪ With the full package, mother-to-child transmission falls from 15–45% to < 1–2%.
▪ India pursues triple elimination of vertical transmission of HIV, syphilis and hepatitis B. [IMPORTANT]
▪ Partner testing and index testing of all family members is an essential part of the package.
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HIV and AIDS (Prevention and Control) Act, 2017 — India [VERY HIGH-YIELD] ▪ Prohibits discrimination against PLHIV and affected persons in employment, education, healthcare, residence, insurance, public office and property rights. ▪ Informed consent is mandatory for HIV testing and treatment (except for screening of donated blood, organs, tissue and semen, and by court order). ▪ Confidentiality is protected; disclosure is permitted only with informed consent or by court order. ▪ No person shall be compelled to disclose their HIV status except by court order. ▪ Requires every state to appoint an Ombudsman to address complaints. ▪ Mandates "as far as possible" provision of ART and management of opportunistic infections by the central and state governments. ▪ Protects the right of a person aged 12 years or above who is sufficiently mature to act as the guardian of a younger sibling and to access their own records. ▪ Prohibits hate propaganda against PLHIV. |
▪ Confidentiality — the cornerstone of trust; breaches deter testing and treatment.
▪ Disclosure — encourage voluntary disclosure to partners with counselling support; assisted partner notification is the preferred model.
▪ Partner notification — voluntary, provider-assisted, or contract referral; involuntary disclosure only under legal authority.
▪ Anti-discrimination — enforced through the Act and through grievance-redressal mechanisms.
▪ Stigma reduction — community education, involvement of PLHIV networks, media engagement and training of healthcare workers (healthcare-setting stigma is a major documented problem in India). [IMPORTANT]
▪ Blood safety — licensed blood banks, mandatory screening, voluntary non-remunerated donation, and haemovigilance.
▪ Community education — the Red Ribbon Clubs in colleges, school AIDS education, and mass-media campaigns under NACP.
▪ Rights of people living with HIV — the right to health, confidentiality, non-discrimination, informed consent, employment, education, marriage, and to found a family.
▪ Ethical principles — autonomy, beneficence, non-maleficence and justice must guide every decision, particularly around testing, disclosure and research participation.
All visual content for this chapter is consolidated here. Each entry states exactly what should be depicted and why it matters for examinations.
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�� Structure of the HIV Virion — Labelled Cross-Section Show: lipid envelope, gp120 and gp41 spikes, p17 matrix, p24 conical capsid, p7 nucleocapsid, two RNA strands, reverse transcriptase, integrase and protease. The single most frequently asked diagram in HIV virology. |
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�� HIV Genome Map — Structural, Regulatory and Accessory Genes Show: 5' LTR, gag, pol, env, tat, rev, nef, vif, vpr, vpu (HIV-1) / vpx (HIV-2), 3' LTR, with the product of each gene labelled. |
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�� HIV Replication Cycle with Drug Targets A 12-step circular diagram from attachment to maturation, with the drug class acting at each step marked alongside — attachment inhibitor, CCR5 antagonist, fusion inhibitor, capsid inhibitor, NRTIs/NNRTIs, INSTIs and PIs. |
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�� CD4 Receptor and Coreceptor Binding — CCR5 versus CXCR4 Tropism Show gp120 binding CD4 with subsequent conformational change exposing the coreceptor binding site; R5 versus X4 tropism and the CCR5-Δ32 deletion. |
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�� Natural History Curve of Untreated HIV Infection The classic dual-axis graph: plasma HIV RNA (peak, set point, late rise) against CD4 count over 10 years, with the acute, latent and AIDS phases and the appearance of opportunistic infections marked. |
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�� Sequence of Appearance of Laboratory Markers (Fiebig Stages) Timeline showing HIV RNA (day 10), p24 antigen (day 14–16), IgM (day 20–25), IgG (day 25–35) and the disappearance of p24 as antibody appears. |
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�� Mechanisms of CD4 T-Cell Depletion Schematic of direct cytopathic effect, syncytium formation, apoptosis, pyroptosis of abortively infected cells, and immune-mediated killing. |
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�� GALT Depletion and Microbial Translocation Gut mucosa before and after HIV infection, showing loss of CD4/Th17 cells, epithelial barrier breach, LPS translocation and systemic immune activation. |
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�� NACO Three-Test HIV Diagnostic Algorithm (Strategy III) Flowchart of A1 → A2 → A3 with outcomes for each combination — positive, negative, indeterminate. |
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�� Early Infant Diagnosis Testing Schedule Timeline from birth PCR through 6 weeks, 6 months, 12 months, 6 weeks after cessation of breastfeeding, and final antibody test at 18 months. |
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�� CD4 Count versus Opportunistic Infection Threshold Chart Vertical CD4 axis from 500 down to 0 with each opportunistic infection placed at its threshold — a single-glance revision figure. |
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�� Approach to a Focal Brain Lesion in HIV Algorithm from imaging through empirical anti-toxoplasma therapy, the 2-week reassessment, and the decision to biopsy. |
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�� Management Algorithm for Fever without Localising Signs in HIV Stepwise flow from stability assessment and TB screening through cultures, imaging and bone-marrow examination. |
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�� NACO Viral-Load Monitoring and Treatment-Failure Algorithm VL > 1000 → enhanced adherence counselling × 3 → repeat VL → switch regimen via SACEP. |
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�� PPTCT Cascade — Maternal Testing to Infant Diagnosis Complete pathway from ANC testing through maternal ART, delivery planning, infant prophylaxis, feeding and EID. |
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�� Post-Exposure Prophylaxis Flowchart First aid → risk assessment → baseline testing → PEP within 72 hours → 28-day regimen → follow-up testing at 6 weeks, 3 and 6 months. |
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�� Oral Candidiasis — Pseudomembranous and Erythematous Forms White curd-like plaques on the buccal mucosa and tongue that scrape off leaving an erythematous base; and the atrophic erythematous form on the palate. A WHO stage 3 marker. |
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�� Oral Hairy Leukoplakia Corrugated, vertically ridged white plaques on the lateral border of the tongue that cannot be scraped off. EBV-related; virtually diagnostic of HIV. |
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�� Kaposi Sarcoma — Cutaneous and Palatal Lesions Violaceous macules, plaques and nodules on the lower limb following skin cleavage lines; and purple palatal/gingival lesions. |
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�� Pruritic Papular Eruption of HIV Symmetrical, excoriated, hyperpigmented papules over the extremities and trunk — very common in Indian and African patients with advanced disease. |
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�� Herpes Zoster — Multidermatomal and Disseminated Forms Vesicles in more than one dermatome, and scattered lesions outside the primary dermatome indicating dissemination. |
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�� Chronic Perianal Herpes Simplex Ulceration Extensive, persistent, painful perianal ulceration lasting more than one month — an AIDS-defining lesion. |
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�� Molluscum Contagiosum — Giant and Multiple Facial Lesions Multiple large umbilicated papules on the face of an adult, indicating advanced immunosuppression. |
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�� Talaromycosis (Penicilliosis) Skin Lesions Umbilicated papules with central necrosis on the face and trunk — mimics molluscum and cryptococcosis. Essential for north-east India. |
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�� Cutaneous Cryptococcosis Umbilicated molluscum-like papules indicating disseminated cryptococcal disease. |
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�� Bacillary Angiomatosis Friable red-purple vascular papules and nodules that bleed easily — the key mimic of Kaposi sarcoma, but curable with antibiotics. |
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�� Seborrhoeic Dermatitis in HIV Greasy erythematous scaling of nasolabial folds, eyebrows and scalp — extensive and refractory. |
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�� Crusted (Norwegian) Scabies Thick hyperkeratotic crusted plaques on the hands, feet and trunk, teeming with mites — highly contagious. |
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�� HIV Lipodystrophy Facial and limb lipoatrophy with buffalo hump and central adiposity — the classic stavudine/zidovudine-era phenotype. |
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�� Severe Cutaneous Adverse Drug Reaction (SJS/TEN) Targetoid lesions with mucosal involvement and epidermal detachment — commonly from nevirapine or cotrimoxazole. |
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�� Oral Kaposi Sarcoma and Necrotising Ulcerative Periodontitis Purple palatal nodules; and rapidly destructive gingival ulceration with bone exposure. |
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�� HIV Wasting Syndrome Marked temporal wasting, loss of subcutaneous fat and muscle bulk — an AIDS-defining condition. |
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�� Chest Radiograph — Pneumocystis jirovecii Pneumonia Bilateral perihilar and diffuse interstitial ground-glass infiltrates with relative apical sparing; may show pneumatoceles and pneumothorax. |
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�� HRCT Chest — Pneumocystis Pneumonia Geographic ground-glass opacification with cyst formation; useful when the chest radiograph is normal. |
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�� Chest Radiograph — Post-Primary Pulmonary Tuberculosis (Preserved Immunity) Upper-lobe infiltrate with cavitation; the classic pattern seen at higher CD4 counts. |
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�� Chest Radiograph — Miliary Tuberculosis Diffuse uniform 1–3 mm nodules throughout both lung fields — the pattern of advanced immunosuppression. |
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�� Chest Radiograph — HIV-TB at Low CD4 Mid- and lower-zone infiltrates with mediastinal and hilar lymphadenopathy, absent cavitation; contrast with the classic adult pattern. |
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�� Chest Radiograph — Lobar Consolidation of Bacterial Pneumonia Dense homogeneous consolidation with air bronchogram. |
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�� Chest Imaging — Pulmonary Kaposi Sarcoma Nodular infiltrates along bronchovascular bundles with pleural effusion and "flame-shaped" opacities. |
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�� Contrast CT/MRI Brain — Cerebral Toxoplasmosis Multiple ring-enhancing lesions in the basal ganglia and at the grey-white junction with marked surrounding oedema and mass effect. |
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�� Contrast MRI Brain — Primary CNS Lymphoma Single periventricular ring- or homogeneously enhancing lesion, often crossing the corpus callosum. |
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�� MRI Brain — Progressive Multifocal Leukoencephalopathy Asymmetrical, non-enhancing, T2/FLAIR-hyperintense white-matter lesions involving subcortical U-fibres, without mass effect. |
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�� MRI Brain — Tuberculous Meningitis Basal meningeal enhancement, hydrocephalus, infarcts and tuberculomas — a critical Indian differential. |
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�� MRI Brain — Cryptococcal Disease Dilated Virchow-Robin spaces ("soap-bubble" gelatinous pseudocysts) and cryptococcomas. |
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�� MRI Brain — HIV Encephalopathy (HAND) Diffuse cerebral atrophy with symmetrical periventricular and deep white-matter T2 hyperintensity without mass effect. |
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�� Ultrasound Abdomen — Abdominal Tuberculosis Enlarged necrotic mesenteric and retroperitoneal nodes, ascites, bowel-wall thickening and splenic microabscesses. |
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�� Barium Swallow / Endoscopy — Oesophageal Candidiasis Shaggy irregular mucosal outline on barium; linear white plaques with ulceration on endoscopy. |
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�� Fundus — CMV Retinitis Perivascular yellow-white areas of retinal necrosis with intraretinal haemorrhage — the "pizza-pie" or "cottage-cheese-and-ketchup" appearance, spreading along the vascular arcades. |
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�� Fundus — HIV Retinopathy Scattered cotton-wool spots without inflammation or haemorrhage; asymptomatic and non-progressive — the key contrast with CMV retinitis. |
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�� Fundus — Toxoplasma Retinochoroiditis Focal necrotising retinitis with overlying dense vitritis — the "headlight in the fog" appearance. |
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�� Fundus — Acute Retinal Necrosis (VZV/HSV) Peripheral confluent retinal whitening with occlusive arteritis and rapid circumferential progression. |
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�� Slit-Lamp — Immune Recovery Uveitis Vitritis, cystoid macular oedema and epiretinal membrane after ART in previously treated CMV retinitis. |
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�� ECG — QT Prolongation from Drug Interaction Prolonged QTc in a patient receiving bedaquiline, moxifloxacin or a macrolide with a protease inhibitor — mandates monitoring. |
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�� ECG — Low-Voltage Complexes with Electrical Alternans The classic pattern of large pericardial effusion, most often tuberculous in Indian PLHIV. |
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�� ECG — Acute Coronary Syndrome in a Young PLHIV ST-segment elevation in a patient in the fourth decade — illustrating premature atherosclerosis in HIV. |
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�� Echocardiography — Large Pericardial Effusion with Tamponade Circumferential echo-free space with diastolic right atrial and right ventricular collapse and IVC plethora. |
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�� Echocardiography — Dilated Cardiomyopathy of HIV Four-chamber view with dilated left ventricle and globally reduced ejection fraction. |
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�� Echocardiography — Tricuspid Valve Vegetation Right-sided infective endocarditis in a person who injects drugs. |
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�� Echocardiography — Pulmonary Arterial Hypertension Dilated right ventricle, flattened interventricular septum ("D-shaped" LV) and raised estimated pulmonary artery systolic pressure. |
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�� Ziehl-Neelsen Stain — Mycobacterium tuberculosis Slender beaded red acid-fast bacilli against a blue background in sputum. Essential for every examination. |
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�� Acid-Fast Stain of Tissue — Mycobacterium avium Complex Foamy macrophages packed with abundant acid-fast bacilli, with poorly formed granulomas — contrast with the well-formed caseating granulomas of tuberculosis. |
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�� India Ink Preparation — Cryptococcus neoformans Round budding yeasts surrounded by a clear unstained capsular halo in CSF. |
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�� Grocott Methenamine Silver Stain — Pneumocystis jirovecii Crushed ping-pong-ball-shaped cysts, 4–7 µm, in a foamy alveolar exudate from BAL fluid. |
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�� Modified Acid-Fast (Kinyoun) Stain — Cryptosporidium Oocysts Round-to-oval 4–6 µm bright pink oocysts against a blue-green background in stool. |
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�� Modified Acid-Fast Stain — Cystoisospora belli Large (20–30 µm) oval oocysts containing sporoblasts; contrast the size with Cryptosporidium and Cyclospora. |
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�� Autofluorescence Microscopy — Cyclospora cayetanensis Blue-green autofluorescent 8–10 µm oocysts under ultraviolet illumination. |
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�� Modified Trichrome (Weber) Stain — Microsporidia Small (1–3 µm) pink-red spores with a characteristic transverse belt-like stripe. |
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�� Wet Mount / Culture — Talaromyces marneffei Intracellular yeast-like cells dividing by transverse fission — NOT budding; and the diffusible red pigment on Sabouraud agar at 25 °C. |
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�� Giemsa Stain — Histoplasma capsulatum in Macrophages Small (2–4 µm) intracellular yeasts within macrophages on a peripheral smear or bone-marrow aspirate. |
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�� KOH Mount / Gram Stain — Candida albicans Budding yeasts with pseudohyphae from an oral scraping. |
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�� Lactophenol Cotton Blue — Aspergillus fumigatus Septate hyphae with conidiophores bearing uniseriate phialides and chains of conidia. |
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�� Giemsa Stain — Leishman-Donovan Bodies Amastigotes within macrophages in a splenic or bone-marrow aspirate — for HIV-visceral leishmaniasis coinfection in the Bihar-Jharkhand belt. |
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�� Dark-Field Microscopy — Treponema pallidum Motile spiral organisms from a chancre exudate. |
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�� Modified Kinyoun Stain — Nocardia species Weakly acid-fast, branching, beaded filaments from sputum or abscess pus. |
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�� Lymph Node — Caseating Granuloma of Tuberculosis Epithelioid cell granuloma with Langhans giant cells and central caseous necrosis. |
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�� Lymph Node — Follicular Hyperplasia and Involution in HIV Early explosive follicular hyperplasia with follicle lysis, progressing to follicular involution and lymphocyte depletion in late disease. |
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�� Colonic Biopsy — CMV Colitis with Owl-Eye Inclusions Large endothelial and stromal cells with basophilic intranuclear inclusions surrounded by a clear halo, plus cytoplasmic inclusions. |
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�� Skin Biopsy — Kaposi Sarcoma Spindle-cell proliferation forming slit-like vascular spaces with extravasated erythrocytes and haemosiderin deposition; LANA-1 immunohistochemistry positive. |
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�� Skin Biopsy — Bacillary Angiomatosis with Warthin-Starry Stain Lobular capillary proliferation with neutrophilic debris; clumps of black-staining bacilli on silver stain. |
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�� Brain — Progressive Multifocal Leukoencephalopathy Demyelination with bizarre enlarged astrocytes and oligodendrocytes containing ground-glass intranuclear inclusions. |
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�� Brain — Toxoplasma Encephalitis Necrotising abscess with free tachyzoites and encysted bradyzoites at the periphery. |
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�� Kidney Biopsy — HIV-Associated Nephropathy Collapsing focal segmental glomerulosclerosis with visceral epithelial cell hypertrophy, microcystic tubular dilatation and interstitial inflammation. |
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�� Lymph Node — Multicentric Castleman Disease (Plasma-Cell Variant) Regressed germinal centres with onion-skin mantle zones and marked interfollicular plasmacytosis; HHV-8 LANA positive. |
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�� Lymph Node / Effusion — HIV-Associated Lymphoma Diffuse large B-cell lymphoma sheets; Burkitt lymphoma with a "starry-sky" pattern; and plasmablastic lymphoma of the oral cavity (CD20-negative, CD138-positive). |
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�� Bone Marrow — Disseminated Infection in HIV Granulomas, haemophagocytosis, and organisms of MAC, Histoplasma, Talaromyces or Leishmania on marrow aspirate and biopsy. |
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�� Oesophageal Biopsy — HSV versus CMV Oesophagitis HSV: multinucleate giant cells with Cowdry type A inclusions at the ulcer margin. CMV: owl-eye inclusions in the ulcer base — the distinction determines therapy. |
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Viva — Virology ▪ Which family and genus does HIV belong to? Retroviridae, subfamily Orthoretrovirinae, genus Lentivirus. ▪ Name the three enzymes carried within the HIV virion. Reverse transcriptase, integrase and protease. ▪ Which HIV gene is unique to HIV-1 and which to HIV-2? vpu is unique to HIV-1; vpx to HIV-2. ▪ What is the function of Nef? Downregulates CD4 and MHC class I, enhancing immune evasion and virulence. ▪ What is the CCR5-Δ32 mutation and its clinical significance? A 32-bp deletion producing a non-functional coreceptor; homozygotes are largely resistant to R5-tropic HIV; the basis of the Berlin and London patient cures and of maraviroc. ▪ Why is HIV so genetically variable? Error-prone reverse transcriptase with no proofreading, enormous daily turnover, and recombination between the two RNA copies. ▪ Which is the irreversible step in the replication cycle? Integration of proviral DNA into the host genome. ▪ What is the viral set point and why does it matter? The stable plasma viral load ~6 months after seroconversion; the strongest single predictor of the rate of progression. |
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Viva — Diagnosis ▪ What are the three "C"s of HIV testing? Consent, Confidentiality, Counselling. ▪ What is the window period and which test shortens it most? The interval between infection and detectability; HIV RNA (~10 days) is the earliest, then p24/4th-generation assays (~15–20 days). ▪ Why can't you diagnose HIV in a 3-month-old infant with an antibody test? Maternal IgG persists up to 18 months — use HIV DNA or RNA PCR. ▪ When is the final confirmatory antibody test done in an HIV-exposed infant? At 18 months, and 6 weeks after complete cessation of breastfeeding for PCR. ▪ What are NACO testing Strategies I, II, IIA and III used for? I — donor screening; II — surveillance; IIA — diagnosis in symptomatic persons; III — diagnosis in asymptomatic persons. ▪ Why must the three tests use different antigen preparations? To avoid repeating the same false-positive reaction. ▪ Define advanced HIV disease. CD4 < 200 cells/µL or WHO stage 3/4 (and all children under 5 not already stable on ART). ▪ Define virological failure. Viral load > 1000 copies/mL on two consecutive measurements at least 3 months apart, with adherence support. |
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Viva — Opportunistic Infections ▪ What is the commonest opportunistic infection and cause of death in Indian PLHIV? Tuberculosis, at any CD4 count. ▪ At what CD4 counts do PCP, toxoplasmosis, cryptococcosis, CMV and MAC occur? < 200, < 100, < 100, < 50 and < 50 respectively. ▪ How is PCP diagnosed and treated? Grocott/immunofluorescence on induced sputum or BAL; cotrimoxazole 15–20 mg/kg/day of TMP for 21 days, with steroids if PaO₂ < 70 mmHg. ▪ Why must folinic acid, not folic acid, be given with pyrimethamine? Folinic acid rescues host marrow without antagonising the antiparasitic effect; folic acid would reverse the drug's action. ▪ Why do we not use mannitol or steroids for raised pressure in cryptococcal meningitis? They are ineffective and steroids increase mortality — serial therapeutic lumbar punctures are the correct treatment. ▪ Which two opportunistic infections require ART to be deliberately delayed? Cryptococcal meningitis (4–6 weeks) and tuberculous meningitis (4–8 weeks). ▪ How do you distinguish cerebral toxoplasmosis from primary CNS lymphoma? Multiple versus single lesions, positive versus negative Toxoplasma IgG, CSF EBV DNA, thallium avidity, and response to a 2-week therapeutic trial. ▪ What is the treatment of cryptosporidiosis? There is no reliably effective specific drug — effective ART with immune reconstitution is the treatment; nitazoxanide is adjunctive. ▪ Which fungus divides by fission rather than budding? Talaromyces marneffei — endemic in north-east India. |
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Viva — ART ▪ What is the first-line ART regimen under NACP? TLD — tenofovir + lamivudine + dolutegravir, one tablet once daily, free of cost. ▪ How do you manage ART in a patient starting rifampicin? Double dolutegravir to 50 mg twice daily; efavirenz needs no change; protease inhibitors are contraindicated (substitute rifabutin). ▪ When do you start ART in a patient with HIV and pulmonary TB? Within 2 weeks if CD4 < 50; within 8 weeks otherwise. ▪ Which drug requires HLA-B*57:01 testing and why? Abacavir — to prevent a potentially fatal hypersensitivity reaction; never rechallenge. ▪ Why does dolutegravir raise the serum creatinine? It blocks tubular creatinine secretion without reducing true GFR — a benign, non-progressive rise. ▪ Why must dolutegravir be separated from antacids, calcium and iron? Polyvalent cations chelate the drug — give DTG 2 hours before or 6 hours after. ▪ What is M184V and why is lamivudine sometimes retained despite it? Lamivudine/emtricitabine resistance mutation; it reduces viral fitness and increases tenofovir/zidovudine susceptibility. ▪ What must you check before stopping or switching ART? HBsAg — withdrawal of tenofovir/lamivudine can precipitate a fatal hepatitis B flare. ▪ What is IRIS and how is it managed? Paradoxical inflammatory deterioration after ART; continue ART and OI therapy, add NSAIDs or corticosteroids, drain collections. |
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Viva — Prevention and Programme ▪ What is the PEP regimen and time window? TDF + 3TC + DTG for 28 days, started ideally within 2 hours and always within 72 hours. ▪ Why is nevirapine avoided for PEP? Risk of severe hepatotoxicity and rash in HIV-negative individuals. ▪ What is U = U? A person with sustained viral load below 200 copies/mL does not transmit HIV sexually. ▪ Which vaccines are contraindicated when CD4 < 200? All live vaccines — BCG, oral polio, MMR, varicella, live zoster, yellow fever, oral typhoid, intranasal influenza. ▪ What is the recommended infant feeding practice in India for an HIV-positive mother on ART? Exclusive breastfeeding for 6 months; mixed feeding must be avoided. ▪ What are the components of the advanced HIV disease package of care? TB screening with LF-LAM, CrAg screening, cotrimoxazole prophylaxis, TB preventive therapy, rapid ART (with the two exceptions), and intensified follow-up. ▪ Name three key provisions of the HIV/AIDS Act 2017. Prohibition of discrimination, mandatory informed consent and confidentiality, and appointment of an Ombudsman in every state. ▪ What is the mode of delivery for a pregnant woman with HIV? Vaginal delivery if viral load < 1000 copies/mL; elective caesarean at 38 weeks if > 1000 or unknown. ▪ Which key population has the highest HIV prevalence in India? People who inject drugs. |
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EPIDEMIOLOGY AND VIROLOGY — MUST-KNOW FACTS First HIV case in India: 1986, Chennai (Dr Suniti Solomon) in female sex workers India has the third largest HIV burden globally; adult prevalence ≈ 0.2% Predominant subtype in India: HIV-1 subtype C (~90–95%); CRF01_AE in the north-east Commonest route of transmission in India: heterosexual sex (~85–88%) Highest prevalence key population in India: people who inject drugs Highest-prevalence states: Mizoram, Nagaland, Manipur, Meghalaya HIV-1 groups: M (pandemic), N, O, P — only M causes the pandemic HIV-1 from SIVcpz (chimpanzee); HIV-2 from SIVsm (sooty mangabey) HIV-2 is intrinsically resistant to all NNRTIs and to enfuvirtide Primary receptor CD4; coreceptors CCR5 (early, R5) and CXCR4 (late, X4) vpu = HIV-1 only; vpx = HIV-2 only p24 = capsid protein, the marker of early infection; gp120 attaches, gp41 fuses Reverse transcriptase is error-prone with no proofreading → quasispecies and resistance Integration is the irreversible step; protease acts at maturation, not entry |
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TRANSMISSION AND PREVENTION — MUST-KNOW FACTS Highest risk route: blood transfusion (~90–95%) Needlestick injury ≈ 0.3%; mucosal splash ≈ 0.09% Receptive anal (~1.4%) > needle sharing (~0.7%) > receptive vaginal (~0.08%) Vertical transmission untreated 15–45%; with full PPTCT < 1–2% Largest component of vertical transmission is intrapartum Mixed feeding carries higher risk than exclusive breastfeeding Transmitting fluids: blood, semen, vaginal and rectal secretions, breast milk HIV is NOT transmitted by mosquitoes, saliva, sweat, tears, urine or casual contact PEP within 72 hours (ideally 2 hours), TDF + 3TC + DTG for 28 days Never use nevirapine for PEP PrEP = TDF/FTC daily; event-driven 2-1-1 only for anal exposure U = U — undetectable equals untransmittable (VL < 200 copies/mL) HPTN 052: 96% reduction in transmission with early ART Male circumcision reduces female-to-male transmission by ~60% |
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DIAGNOSIS AND STAGING — MUST-KNOW FACTS Order of marker appearance: RNA (day 10) → p24 (day 14–16) → IgM → IgG 4th-generation assay = p24 antigen + antibody; window ~15–20 days NACO Strategy III = three tests with different antigens for asymptomatic diagnosis Infant diagnosis under 18 months requires DNA/RNA PCR — antibody is maternal EID schedule: 6 weeks, then per protocol, 6 weeks after stopping breastfeeding, antibody at 18 months WHO staging = clinical; CDC staging = CD4-based surveillance AIDS = CD4 < 200 or any AIDS-defining illness Advanced HIV disease = CD4 < 200 or WHO stage 3/4 Virological failure = VL > 1000 copies/mL twice, ≥ 3 months apart, with adherence support Viral load is the gold standard for monitoring; CD4 % is used in children < 5 years A low-positive HIV RNA (< 5000) with negative serology may be a false positive — repeat |
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OPPORTUNISTIC INFECTIONS — MUST-KNOW FACTS CD4 < 200 → PCP; < 100 → toxoplasmosis and cryptococcosis; < 50 → CMV and MAC TB occurs at ANY CD4 count and is the commonest OI and cause of death in India Up to 20% of HIV-TB have a normal chest X-ray; CBNAAT is the first-line test Urine LF-LAM is recommended when CD4 < 200 or the patient is seriously ill PCP: dry cough, exertional desaturation, normal chest signs, raised LDH PCP steroids if PaO₂ < 70 mmHg or A-a gradient > 35 mmHg, within 72 hours Cryptococcal meningitis: neck stiffness often ABSENT; CSF CrAg > 95% sensitive Serial therapeutic LPs — NOT mannitol or steroids — for raised ICP in cryptococcosis Delay ART 4–6 weeks in cryptococcal meningitis; 4–8 weeks in TB meningitis Toxoplasmosis: multiple ring-enhancing lesions; pyrimethamine + sulfadiazine + FOLINIC acid Primary CNS lymphoma: single lesion, EBV DNA in CSF, thallium-avid, 100% EBV-related PML: non-enhancing white-matter lesions, no fever, JC virus PCR; only treatment is ART CMV retinitis: "pizza-pie" fundus at CD4 < 50; valganciclovir MAC: CD4 < 50, fever, anaemia, raised ALP; clarithromycin + ethambutol Cryptosporidium: no effective specific drug — ART is the treatment Cystoisospora and Cyclospora: cotrimoxazole works Talaromyces marneffei: divides by FISSION; red pigment; north-east India Oral hairy leukoplakia = EBV, non-scrapable, lateral tongue |
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ART AND DRUG SAFETY — MUST-KNOW FACTS NACP first line: TLD = Tenofovir + Lamivudine + Dolutegravir, free, once daily Treat All — ART for everyone at any CD4, any stage, including pregnancy Rifampicin → dolutegravir 50 mg TWICE daily; efavirenz unchanged; PIs contraindicated Tenofovir → nephrotoxicity and Fanconi syndrome and bone loss Zidovudine → macrocytic anaemia and neutropenia Abacavir → hypersensitivity; check HLA-B*57:01; NEVER rechallenge Nevirapine → hepatotoxicity and SJS; avoid if CD4 > 250 (women) or > 400 (men) Efavirenz → CNS effects, vivid dreams, take at bedtime on an empty stomach Atazanavir → benign unconjugated hyperbilirubinaemia; needs gastric acid (no PPIs) Dolutegravir → weight gain, insomnia, benign creatinine rise Separate dolutegravir from antacids, calcium and iron by 2 hours before / 6 hours after Avoid simvastatin and lovastatin with protease inhibitors St John's wort is contraindicated with all ART HBV coinfection → regimen MUST contain tenofovir + lamivudine; never stop abruptly Never add a single active drug to a failing regimen (functional monotherapy) M184V reduces viral fitness and increases tenofovir susceptibility — often retained |
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SPECIAL SITUATIONS AND PUBLIC HEALTH — MUST-KNOW FACTS Pregnancy: TLD at any gestation; dolutegravir is safe (neural-tube concern not confirmed) Vaginal delivery if VL < 1000; elective LSCS at 38 weeks if VL > 1000 or unknown Infant: nevirapine syrup 6 weeks (12 weeks dual if high risk) + cotrimoxazole from 6 weeks Exclusive breastfeeding for 6 months — never mixed feeding Adolescents have the worst viral suppression of any age group Live vaccines contraindicated at CD4 < 200; BCG contraindicated in HIV-infected infants Recombinant zoster vaccine (Shingrix) is safe; live zoster vaccine is not Cotrimoxazole prophylaxis at CD4 < 200; stop when CD4 > 200 for 3–6 months TB preventive therapy (6H) for ALL PLHIV once active TB is excluded Serum CrAg screening for ALL with CD4 < 200 HIV/AIDS Act 2017: no discrimination, informed consent, confidentiality, state Ombudsman Consent for testing from age 12 years if sufficiently mature UNAIDS target 95-95-95 by 2025; end AIDS as a public-health threat by 2030 HIV is no longer a contraindication to renal transplantation when suppressed |
End of HIV Infection & AIDS — Medicine Study Notes
MedMentor EDU | Prepared for MBBS, NEET-PG, INI-CET, DNB and FMGE | Best of luck in your exams!
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