Discuss the aetiology, transmission, natural history, clinical features, diagnosis and staging of HIV infection.

Aetiology

HIV is an enveloped, single-stranded RNA retrovirus of the lentivirus genus. HIV-1 causes the global pandemic; HIV-2, largely confined to West Africa (with pockets in western India), is less transmissible, progresses more slowly and is intrinsically resistant to NNRTIs — a fact that changes treatment.

Structure and replication: the virus carries three key enzymes — reverse transcriptase, integrase and protease — each of which is a drug target. The envelope glycoprotein gp120 binds the CD4 receptor, with CCR5 or CXCR4 as co-receptors, on CD4+ T-helper lymphocytes, macrophages, monocytes and dendritic cells. Reverse transcriptase converts viral RNA to DNA, which integrates into the host genome as provirus — establishing a latent reservoir that current therapy cannot eradicate, and which is the reason HIV is not curable.

Transmission

Natural History

1. Acute (primary) infection — 2–6 weeks after exposure: a transient seroconversion illness with a very high viral load and steep fall in CD4 count (see the separate answer).

2. Clinical latency — a partially effective immune response controls viraemia to a "set point"; the patient is asymptomatic but the virus replicates continuously, destroying CD4 cells. Lasts a median of 8–10 years untreated.

3. Symptomatic HIV — as CD4 falls below about 350–500/µL: constitutional symptoms, minor opportunistic conditions, oral candidiasis, herpes zoster.

4. AIDS — CD4 below 200/µL or the occurrence of an AIDS-defining illness.

Progression is not uniform: "rapid progressors" reach AIDS within 2–3 years; "long-term non-progressors" and "elite controllers" (with protective HLA types or CCR5-delta32 heterozygosity) maintain counts for many years.

CLINICAL FEATURES BY STAGE (WHO clinical staging)

System-wise manifestations: oral (candidiasis, hairy leucoplakia, periodontitis, Kaposi's sarcoma); respiratory (tuberculosis — the commonest opportunistic infection and leading cause of death in India, PCP, bacterial pneumonia); gastrointestinal (chronic diarrhoea from cryptosporidium, isospora, MAC; oesophageal candidiasis); neurological (see the opportunistic infections answer); dermatological; haematological (anaemia, cytopenias, lymphoma); and renal (HIV-associated nephropathy).

Diagnosis

• Screening: third or fourth generation ELISA. Fourth-generation assays detect p24 antigen as well as antibody, shortening the window period to about 2–3 weeks (compared with 4–12 weeks for antibody-only tests).
• India's national testing strategy uses three rapid tests based on different antigens or principles — a reactive result on the first is confirmed by two further tests before the patient is declared positive.
• Western blot is no longer routinely used in most algorithms.
• HIV RNA (viral load) by PCR — for diagnosis in the window period, in acute HIV infection (antibody negative, RNA positive), in infants under 18 months (where maternal antibody persists and DNA/RNA PCR is required), and for monitoring therapy.
• CD4 count — for staging, assessing prophylaxis needs and monitoring immune recovery.
• Baseline workup after diagnosis: CBC, renal and liver function, fasting glucose and lipids, hepatitis B and C serology, VDRL/RPR, tuberculosis screening (symptom screen, chest X-ray, CBNAAT where indicated), cryptococcal antigen if CD4 is very low, pregnancy test, and HLA-B*5701 where abacavir is planned.

Pre-test and post-test counselling with informed consent and strict confidentiality is mandatory, and testing must be voluntary.

Principles of Management

• Start antiretroviral therapy in ALL people living with HIV, regardless of CD4 count — the "test and treat" policy, which improves individual outcomes and, by achieving viral suppression, prevents onward transmission (U = U: undetectable equals untransmittable).
• Opportunistic infection prophylaxis — co-trimoxazole based on CD4 count and clinical stage; isoniazid preventive therapy / TB preventive therapy after excluding active disease.
• Screening and management of comorbidity — tuberculosis, hepatitis B and C, sexually transmitted infections, cervical cancer screening, cardiovascular and metabolic risk.
• Prevention of mother-to-child transmission — ART for all pregnant women, safe delivery practices, infant prophylaxis and infant feeding counselling.
• Prevention: condom promotion, treatment of STIs, needle and syringe programmes and opioid substitution for people who inject drugs, blood safety, pre-exposure prophylaxis (PrEP) for high-risk individuals, post-exposure prophylaxis, and voluntary medical male circumcision.
• Psychosocial support, adherence counselling, nutrition, and addressing stigma — in India, stigma and disclosure fears are among the biggest determinants of whether a patient stays in care.