Bit · Micro
HIV Stages and Opportunistic Infections by CD4 Count
HIV progression is staged by CD4 count, and each CD4 threshold unlocks a new set of opportunistic infections. Know the count, predict the infection.
Mechanism
HIV is a retrovirus (single-stranded RNA, reverse transcribed to DNA, integrated by integrase). It infects CD4 T cells via gp120 binding (CCR5 or CXCR4 coreceptor). Disease progression follows CD4 count:
- Acute HIV (weeks 2–4) — viral syndrome (fever, sore throat, lymphadenopathy, rash, mononucleosis-like). Very high viral load. Antibody often negative early — diagnose with HIV RNA or 4th-gen Ag/Ab test.
- Clinical latency (years) — asymptomatic or persistent generalized lymphadenopathy. CD4 slowly declines.
- AIDS — CD4 < 200 OR an AIDS-defining illness regardless of count.
Differentiator Table
| CD4 count | Opportunistic infections / conditions | Prophylaxis |
|---|---|---|
| Any CD4 | Kaposi sarcoma (HHV-8), TB, herpes zoster, oral hairy leukoplakia (EBV), bacterial pneumonia, candidal vaginitis | |
| < 500 | Recurrent thrush, recurrent shingles, Kaposi sarcoma, lymphoma, ITP, HIV nephropathy | |
| < 200 | PCP (Pneumocystis jirovecii) — diffuse interstitial 'bat-wing' infiltrates, ↑ LDH | TMP-SMX |
| < 200 | Toxoplasma — multiple ring-enhancing brain lesions | |
| < 100 | Cryptococcus neoformans — meningitis with India-ink stain, capsule, ↑ opening pressure | Fluconazole if past episode |
| < 100 | Histoplasma capsulatum — disseminated; ↓ Toxoplasma with TMP-SMX prophylaxis | |
| < 50 | CMV — retinitis ('pizza-pie'), esophagitis (large solitary ulcers), colitis | Routine ophthalmology surveillance |
| < 50 | MAC (Mycobacterium avium complex) — disseminated fever, weight loss, anemia | Azithromycin weekly |
| < 50 | Cryptosporidium — chronic watery diarrhea | |
| < 50 | Primary CNS lymphoma (EBV-driven) — solitary ring-enhancing lesion (vs Toxo's multiple) |
The Pivot
Three counts unlock most NBME questions:
- < 200 → PCP. Start TMP-SMX prophylaxis. Treat established PCP with high-dose TMP-SMX + steroids if pO₂ < 70.
- < 100 → Cryptococcal meningitis + Toxoplasma encephalitis.
- < 50 → CMV retinitis + MAC.
Treatment of HIV itself: ART regimens are typically 2 NRTIs + integrase inhibitor (e.g. tenofovir + emtricitabine + dolutegravir / bictegravir).
NBME-Style Stem
A 34-year-old man with untreated HIV (CD4 count 38/mm³) presents with seizures and right-sided hemiparesis. Brain MRI shows multiple ring-enhancing lesions at the gray-white junction and in the basal ganglia. Toxoplasma serology is positive. Which of the following is the most appropriate initial therapy?
Concept Anchor
HIV destroys CD4 cells progressively; each CD4 threshold unlocks a different opportunistic infection. The CD4 count alone predicts the differential before you see the patient.