HIV Infection and AIDS
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Direct answer
CD4 T-lymphocyte depletion explains nearly every manifestation of HIV infection, from the persistent generalised lymphadenopathy of early disease to the opportunistic infections and cancers that define AIDS at counts below 200 per microlitre. The virus bears gp120, which binds CD4 with the co-receptors CCR5 (transmitted strains) and CXCR4 (later, syncytium-inducing strains), and reverse-transcribes its RNA into proviral DNA that integrates into the host genome. India's national programme (NACO) treats all patients regardless of CD4 count, and tuberculosis remains the commonest opportunistic infection and killer.
What you must remember
- Entry biology: gp120 binds CD4 then CCR5 or CXCR4; gp41 mediates fusion; people homozygous for the CCR5-delta32 mutation are largely resistant to infection — the biology behind entry-inhibitor drugs and the cured Berlin patient (CCR5-delta32 stem-cell transplant).
- Retroviral life cycle: reverse transcriptase (RNA to DNA, error-prone, driving rapid resistance), integrase (proviral integration), protease (maturation) — each a drug target.
- Course: acute retroviral syndrome (mononucleosis-like, high viraemia) — clinical latency with ongoing replication — AIDS as CD4 falls below 200; median untreated interval about 8-10 years.
- CD4 milestones: below 500 — oral candidiasis, Kaposi sarcoma can appear; 200-500 — pulmonary and extrapulmonary tuberculosis, Pneumocystis pneumonia risk begins below 200; below 200 — Pneumocystis jirovecii pneumonia, toxoplasmosis, cryptosporidiosis, oesophageal candidiasis; below 100 — cryptococcal meningitis, microsporidiosis; below 50 — CMV retinitis, disseminated Mycobacterium avium complex, primary CNS lymphoma.
- AIDS-defining cancers: Kaposi sarcoma (HHV-8, spindle-cell vascular tumour), aggressive B-cell non-Hodgkin lymphomas (including CNS and effusion lymphomas), invasive cervical carcinoma (HPV); anal and Hodgkin lymphoma are non-defining but strongly associated.
- Lymph node histology: florid follicular hyperplasia with giant follicles early, progressing to involution and depletion — the node mirrors the CD4 curve; lamina propria depletion explains chronic diarrhoea.
- Central nervous system pathology: HIV encephalitis with microglial nodules, multinucleated giant cells and white-matter pallor — HIV-associated neurocognitive disorder; vacuolar myelopathy and distal symmetric polyneuropathy.
- Diagnosis: fourth-generation antigen-antibody combination assays; viral load for infant diagnosis (maternal antibodies persist) and for monitoring; elite controllers suppress viraemia without drugs.
- Treatment: antiretroviral therapy for all regardless of CD4 count (treat-all policy under NACO), standard first-line regimens built on two nucleoside analogues plus an integrase inhibitor or non-nucleoside reverse-transcriptase inhibitor; ART for life, with immune reconstitution inflammatory syndrome (IRIS) a recognised early hazard — paradoxical worsening as immunity returns, classically around tuberculosis.
- Prevention of mother-to-child transmission: triple-drug ART in pregnancy plus peripartum and neonatal prophylaxis has cut transmission to low single digits where programmes function.
Reading the natural history through one patient's counts
A 28-year-old presents with six weeks of fever, rash and sore throat after an unprotected exposure: acute retroviral syndrome, viral load in the millions, antibody test just turning positive. Over the following years his CD4 drifts from 700 to 380 while he feels well — clinical latency is misnamed, because billions of virions turn over daily and gut-associated lymphoid tissue loses most of its CD4 memory cells first.
At CD4 190 he develops dry cough and progressive dyspnoea — Pneumocystis pneumonia, its cup-shaped cysts on silver or immunofluorescent staining of induced sputum. At CD4 80, headache with a positive cryptococcal antigen on CSF, India ink showing encapsulated budding yeasts. At CD4 40, floaters lead to a fundus showing haemorrhagic retinitis with perivascular necrosis — cytomegalovirus, treated with ganciclovir. Prophylaxis follows the same logic: cotrimoxazole below 200 (also protecting against toxoplasmosis), azithromycin below 50 for MAC in high-prevalence settings.
The pathology bench sees his lymph node during latency — explosive follicular hyperplasia with serpiginous follicles and multinucleated giant cells — and years later burnt-out, hyalinised follicles with scant lymphocytes: depletion, the histological correlate of the falling count.
He then starts ART under the treat-all policy; two weeks later his tuberculosis lesions paradoxically swell — immune reconstitution inflammatory syndrome — managed with corticosteroids while continuing both ART and antitubercular therapy.
Where students slip
Three errors recur. First, AIDS is defined immunologically by CD4 below 200 or by an AIDS-defining illness — candidates wait for clinical cachexia before labelling AIDS and misanswer staging questions. Second, the co-receptor switch is confused: CCR5-tropic strains transmit and dominate early; CXCR4-tropic strains emerge later, are syncytium-inducing, and herald faster decline. Third, IRIS is misread as treatment failure or new infection: it occurs within weeks of ART as immunity recovers against antigens of organisms already present, and the management is prednisone-based control with continued therapy. Finally, in the Indian framing every HIV-positive patient is screened for tuberculosis, the commonest opportunistic infection and cause of death — the two national programmes are entwined.
Frequently asked questions
Which viral glycoprotein and receptors mediate HIV entry?
gp120 binding CD4 followed by CCR5 or CXCR4 engagement, with gp41-driven membrane fusion.
Why is viral load rather than antibody testing used in infants?
Maternal IgG crosses the placenta and confuses antibody assays, so proviral DNA or RNA PCR is diagnostic in babies.
Which pneumonia is characteristic at CD4 counts below 200?
Pneumocystis jirovecii pneumonia, with ground-glass infiltrates and cup-shaped cysts on silver staining of lavage fluid.
Which three tumours are AIDS-defining?
Kaposi sarcoma, aggressive B-cell non-Hodgkin lymphomas and invasive cervical carcinoma, driven by HHV-8, EBV-related mechanisms and HPV respectively.
What is the immune reconstitution inflammatory syndrome?
Paradoxical worsening of existing opportunistic infections or autoimmune phenomena within weeks of starting ART as immune function recovers, treated with corticosteroids while continuing therapy.
What is the current ART initiation policy under India's national programme?
Treat-all: antiretroviral therapy for every HIV-positive person regardless of CD4 count or clinical stage, with lifelong adherence and viral-load monitoring.