HIV opportunistic infections
in review
5 min read
Updated 2026-09-29
HIV opportunistic infections
CD4 count predicts which OIs are possible. Primary prophylaxis: TMP-SMX for PJP at CD4 <200 (and toxoplasma at <100 if IgG-positive); screen serum CrAg at CD4 <100. PJP with PaO₂ <9.3 kPa → adjunctive prednisone. Cryptococcal meningitis: amphotericin + flucytosine, daily therapeutic LPs for raised pressure, and delay ART 4–6 weeks. For most other OIs start ART within 2 weeks (ACTG A5164 (2009)).
do not miss
- cryptococcal meningitis with opening pressure >25 cm H₂O → daily therapeutic LP; raised pressure drives early death
- PJP with hypoxaemia → start steroids with the first TMP-SMX dose, not after deterioration
- ring-enhancing lesions not improving by 10–14 days of toxoplasma therapy → biopsy for CNS lymphoma
differential by CD4 count
| CD4 (× 10⁶/L) | typical infections |
|---|---|
| any | bacterial pneumonia, TB, zoster, syphilis, Kaposi sarcoma, lymphoma |
| <200 | PJP, oesophageal candidiasis, disseminated histoplasmosis/coccidioidomycosis |
| <100 | toxoplasma encephalitis, cryptococcal meningitis |
| <50 | CMV retinitis/colitis, disseminated MAC, primary CNS lymphoma |
| any (usually <200) | PML (JC virus) |
primary prophylaxis
| pathogen | start | regimen | stop |
|---|---|---|---|
| PJP | CD4 <200, CD4 <14%, or oral thrush | TMP-SMX 1 DS or 1 SS daily (alt: dapsone — check G6PD; atovaquone) | CD4 >200 for ≥3 months on ART (or 100–200 with suppressed HIV RNA ≥3–6 months) |
| toxoplasma | CD4 <100 + IgG-positive | TMP-SMX 1 DS daily (alt: dapsone + pyrimethamine + leucovorin) | CD4 >200 for ≥3 months |
| MAC | — | not recommended if ART started immediately | — |
| cryptococcus | CD4 <100 → serum CrAg | CrAg-positive → LP; if CSF negative → pre-emptive high-dose fluconazole | — |
| TB | positive IGRA/TST (≥5 mm) | treat TB infection — see tuberculosis | — |
pneumocystis pneumonia (PJP)
- subacute dyspnoea, dry cough, exertional desaturation; bilateral interstitial/ground-glass infiltrates (CXR can be normal); pneumothorax
- diagnosis: induced sputum or BAL PCR/immunofluorescence; β-D-glucan high (supportive); LDH raised
- TMP-SMX 15–20 mg/kg/day (TMP) IV/PO divided q6–8h × 21 days
- adjunctive prednisone if PaO₂ <9.3 kPa on room air or A–a gradient ≥4.7 kPa — start within 72 h: 40 mg BID days 1–5, 40 mg daily days 6–10, 20 mg daily days 11–21
- alternatives: primaquine + clindamycin (G6PD first), IV pentamidine; mild disease — atovaquone or TMP + dapsone
- TMP-SMX toxicity: rash, cytopaenias, hyperkalaemia, creatinine rise (tubular secretion), hepatitis
- secondary prophylaxis after treatment, until CD4 criteria met
cryptococcal meningitis
- subacute headache, fever, altered mentation; meningism often absent
- serum and CSF CrAg (highly sensitive); CSF India ink/culture; always measure opening pressure
- induction: liposomal amphotericin B 3–4 mg/kg IV daily + flucytosine 25 mg/kg PO QID × 2 weeks; AMBITION (2022): single 10 mg/kg liposomal amphotericin + 14 days flucytosine + fluconazole non-inferior with less toxicity (WHO preferred where resources limited)
- consolidation: fluconazole 800 mg daily × 8 weeks → maintenance 200 mg daily ≥1 year, stop once CD4 ≥100 with suppressed HIV RNA ≥3 months
- opening pressure >25 cm H₂O → daily therapeutic LP (to <20 or 50% reduction); no role for steroids, acetazolamide, or mannitol
- delay ART 4–6 weeks — COAT (2014): early ART (1–2 weeks) → higher mortality
toxoplasma encephalitis
- headache, focal deficits, seizures, confusion; CD4 <100; toxoplasma IgG positive (negative IgG makes it unlikely)
- CT/MRI: multiple ring-enhancing lesions, basal ganglia/corticomedullary junction
- pyrimethamine 200 mg load → 50–75 mg daily + sulfadiazine 1–1.5 g q6h + leucovorin 10–25 mg daily, ≥6 weeks; TMP-SMX 5 mg/kg (TMP) BID is an accepted alternative (pyrimethamine access limited)
- dexamethasone only for mass effect
- no clinical/radiological response at 10–14 days → brain biopsy; single lesion + EBV PCR positive in CSF → primary CNS lymphoma
- secondary prophylaxis until CD4 >200 for ≥6 months
CMV, MAC, and other OIs
| OI | clues | treatment |
|---|---|---|
| CMV retinitis | CD4 <50, floaters, visual field loss; retinal haemorrhage + exudate | urgent ophthalmology; valganciclovir 900 mg BID × 14–21 days → 900 mg daily; intravitreal ganciclovir if sight-threatening |
| CMV colitis/oesophagitis | ulcers with inclusion bodies on biopsy | ganciclovir IV → valganciclovir; plasma CMV DNA alone does not mandate treatment |
| disseminated MAC | CD4 <50, fever, weight loss, anaemia, raised ALP; AFB blood cultures | clarithromycin (or azithromycin) + ethambutol ± rifabutin; ≥12 months and CD4 >100 for ≥6 months |
| oesophageal candidiasis | odynophagia ± thrush | fluconazole 200–400 mg × 14–21 days; endoscopy if no response (CMV, HSV) |
| PML | subacute focal deficits; non-enhancing white-matter lesions; JC virus PCR in CSF | ART only |
when to start ART after an OI
| OI | timing |
|---|---|
| most OIs (PJP, toxoplasma, bacterial infections) | within 2 weeks (ACTG A5164) |
| TB, CD4 <50 | within 2 weeks |
| TB, CD4 ≥50 | within 8 weeks |
| TB meningitis | defer ~8 weeks |
| cryptococcal meningitis | defer 4–6 weeks |
| PML, Kaposi sarcoma, MAC | immediately — ART is the treatment |
IRIS
- paradoxical worsening of a known OI, or unmasking of a subclinical one, typically 2–12 weeks after starting ART, with falling HIV RNA and rising CD4
- highest risk: low baseline CD4, high viral load, TB, cryptococcus, MAC, short OI-to-ART interval
- continue ART (except life-threatening CNS IRIS); NSAIDs or prednisone for moderate–severe TB-IRIS
- PredART (2018): prophylactic prednisone for 4 weeks when starting ART (CD4 ≤100, on TB treatment) reduced TB-IRIS
- exclude treatment failure, drug resistance, and a new OI before diagnosing IRIS
traps
- stopping PJP prophylaxis on a single CD4 >200 — needs ≥3 months on ART
- dapsone without G6PD testing → haemolysis
- early ART in cryptococcal or TB meningitis → excess mortality
- treating toxoplasma empirically without checking IgG
- CD4 low but not “that low”: TB, bacterial pneumonia, syphilis, and lymphoma occur at any CD4
- assuming “IRIS” when it is a new OI or drug-resistant TB