General Medicine

DEFINITION & TYPES

IRIS = paradoxical worsening of existing OIs OR unmasking of previously subclinical OIs after starting ART, due to recovery of immune function → exaggerated inflammatory response to antigens (alive or dead pathogens).

• Most common IRIS-associated OIs: TB (#1 — paradoxical IRIS in HIV-TB); Cryptococcal meningitis; CMV; Kaposi's sarcoma (KS-IRIS)
• Risk factors: Low CD4 at ART start (< 50 ); high viral load; rapid VL decline; starting ART within 2 weeks of OI treatment
• Clinical presentation: usually within 4-8 weeks of starting ART; paradoxical worsening of a treated OI or unmasking of a latent one, accompanied by a rising CD4 count and falling viral load; commonly fever, worsening lymphadenopathy and new or worsening organ-specific inflammation.
• Diagnosis: a clinical diagnosis of exclusion - rule out OI treatment failure, drug resistance, a new infection and drug reaction; requires evidence of immune recovery temporally related to ART.
• Management: Continue ART (do NOT stop unless life-threatening); continue OI treatment; NSAIDs for mild; Prednisolone 1 mg/kg/day × 2–4 weeks for severe (especially TB-IRIS); therapeutic LP + fluconazole for Crypto-IRIS (↑ ICP)

• Key thresholds: normal CD4 is 500-1500/uL; < 200 is the AIDS-defining threshold (PCP risk); < 100 - toxoplasma and cryptococcus; < 50 - CMV and MAC; CD4% is used in young children.
• OI prophylaxis: CD4 < 200 - co-trimoxazole (PCP, also covers toxoplasma); CD4 < 100 with positive toxoplasma serology - co-trimoxazole; prophylaxis is stopped once CD4 is sustained above threshold on ART.
• CD4 and immune function: CD4+ T-helper cells coordinate adaptive immunity; as CD4 falls, susceptibility to opportunistic infections increases progressively; routine vaccination should be given early (before CD4 falls < 200) as the immune response is blunted at lower counts.
• India-specific context (NACO): co-trimoxazole prophylaxis for all HIV patients with CD4 < 350 cells/uL or WHO clinical stage 3/4, regardless of CD4; isoniazid preventive therapy (IPT) for 6 months for all HIV patients after ruling out active TB; HBV and pneumococcal vaccines.
• Monitoring: CD4 at baseline and to guide prophylaxis; viral load is the main tool to monitor ART response; CD4 recovers gradually over months on effective therapy.

• Treat ALL HIV-positive individuals regardless of CD4 count (WHO/NACO 2021 Treat-All policy)
• Priority — start WITHIN 2 WEEKS: CD4 < 200; AIDS-defining illness; HIV-TB co-infection; HIV-HBV co-infection; pregnant women; children < 5 yrs; discordant couple
• Same-day ART: All newly diagnosed HIV after ruling out active TB and cryptococcal meningitis (especially if CD4 < 200)

▶ First-line NACO 2021: TDF + 3TC + DTG once daily × lifelong

• Goals of ART: Viral suppression (< 20 copies/mL ) within 6 months; CD4 recovery; prevent OIs; prevent HIV transmission; improve survival and quality of life
• First-line drug classes: a backbone of 2 NRTIs (tenofovir + lamivudine/emtricitabine) plus an integrase inhibitor (dolutegravir, preferred) or an NNRTI (efavirenz); single-tablet regimens improve adherence.
• Baseline and monitoring tests: CD4 count, HIV viral load, FBC, renal and liver function, HBV/HCV serology, TB screen, and cryptococcal antigen if CD4 < 100; check viral load at 6 months (target undetectable) and periodically thereafter.
• Adverse effects and monitoring: tenofovir - nephrotoxicity and bone density loss (monitor eGFR and phosphate); dolutegravir - weight gain, neural tube defects in first trimester (avoid or counsel); efavirenz - CNS side effects, teratogenic; check viral load at 6 months (target < 20 copies/mL); switch regimen if viral load > 1000 copies/mL at 6 months (treatment failure).
• Drug interactions: rifampicin (for TB co-treatment) induces CYP3A4 - use rifabutin with PI-based regimens or use efavirenz with standard rifampicin dose; avoid drugs that prolong QT with some PIs; metformin dose adjustment with dolutegravir.

• Category III exposure (transdermal bites, mucous membrane): Wound washing × 15 min + RIG 20 IU/kg (infiltrate wound + IM remainder) + Rabies vaccine
• Vaccine: VERORAB (cell culture); 5 doses — days 0, 3, 7, 14, 28 (Essen schedule) OR WHO 2018: 3 visits — day 0 (2 ID doses) + day 7 (1 dose) + day 28 (1 dose)
• RIG ONLY on Day 0 — not after day 7; HRIG 20 IU/kg; infiltrate all into wound; remainder IM at different site from vaccine
• No window for PEP — give even late (days after exposure); only contraindicated once symptoms appear (then purely palliative)
• Pre-exposure prophylaxis (PrEP) for veterinarians/travellers to endemic areas: 3 doses (days 0, 7, 21/28); booster every 3–5 years or guided by titres
• Wound categories (WHO): Category I (touching/feeding an animal, intact skin) - no PEP; Category II (minor scratches/abrasions without bleeding) - wound care + vaccine; Category III (transdermal bite, licks on broken skin/mucosa, any bat contact) - wound care + vaccine + RIG.
• Rabies disease: once symptoms appear it is almost universally fatal; presents with hydrophobia, aerophobia and agitation (furious form) or ascending paralysis (paralytic form); treatment is purely palliative - which is why timely PEP is critical.
• Wound management: immediate and thorough wound washing with soap and water for at least 15 minutes is the single most effective step in preventing rabies; povidone-iodine application after washing; do not suture wounds immediately unless essential for haemostasis.
• Pre-exposure prophylaxis: for high-risk groups (veterinarians, animal handlers, travellers to endemic areas, lab workers); 3-dose schedule (days 0, 7 and 21/28); confirm titre response; booster every 2-5 years or on titre check; reduces but does not eliminate the need for post-exposure vaccine after subsequent exposure.

DEFINITION

Acute HIV syndrome = the clinical manifestation of primary HIV infection occurring 2–6 weeks after HIV acquisition when viral replication is explosive and viral load is highest (10⁶–10⁸ copies/mL). Corresponds to initial CD4 drop before immune reconstitution. Also called acute retroviral syndrome or seroconversion illness .

CLINICAL FEATURES

Mononucleosis-like illness (easily mistaken for EBV/CMV mononucleosis or dengue):

• Fever (> 38°C; present in > 90%); pharyngitis (without exudate usually); lymphadenopathy (generalised)
• Rash — maculopapular erythematous rash on trunk/face; non-specific; lasts 5–8 days
• Myalgia; arthralgia; headache; fatigue; night sweats; oral ulcers; genital ulcers
• Neurological (10–20%): Aseptic meningitis; encephalitis; peripheral neuropathy; GBS-like
• GI: Nausea; diarrhoea; weight loss (> 10% = rapid progression risk)

DIAGNOSIS

• HIV-1 RNA (viral load) — positive very early (within 2–11 days of exposure); highest sensitivity during window period
• p24 Antigen — detectable from day 16–18 before antibodies; 4th generation ELISA (Ag/Ab combo ) detects both p24 + antibody
• ELISA may be negative (window period — antibodies not yet formed at 2–3 weeks); repeat at 6 weeks
• Start ART immediately even in acute infection — reduces viral reservoir, prevents CD4 decline, reduces transmission
• Management and significance: infectivity is very high in this phase because of an extremely high viral load; consider acute HIV in anyone with a mononucleosis-like illness and risk factors, offer 4th-generation testing (and HIV RNA in the window period), and arrange partner notification.
• Acute retroviral syndrome features: the viral load is extremely high (millions of copies/mL) and CD4 count transiently falls; this is the peak of infectivity; symptoms last 2-4 weeks and resolve spontaneously; a rash is present in about 50% and oral/genital ulcers in 10-20%.
• Window period: the time between infection and a positive antibody test; 4th generation Ag/Ab combination tests detect infection at 18 days median; HIV RNA detectable at 11 days; inform patients tested during window period to retest at 6 weeks.