HIV/AIDS — CD4 Thresholds, OI Prophylaxis & ART

Creator: Progress Note
Published: 2026-07-22
Keywords: HIV AIDS CD4 count opportunistic infections, HIV OI prophylaxis, antiretroviral therapy regimen, CD4 count AIDS-defining illness, HIV transmission prevention

The 60-second version

CD4 <200: start TMP-SMX (covers PCP + Toxoplasma); CD4 <50: add azithromycin weekly (MAC)
ART for ALL HIV patients; preferred: 2 NRTIs + integrase inhibitor (dolutegravir or bictegravir)
PCP: bilateral interstitial infiltrates, high LDH, TMP-SMX treatment; CMV retinitis: ganciclovir
Toxo: multiple ring-enhancing CNS lesions + positive IgG serology → empiric treatment first
IRIS: paradoxical worsening of OI after starting ART as immune system reconstitutes

Topic Cluster

All Infectious Disease Resources

Pneumonia Organisms for USMLE: CAP vs HAP, Atypicals, and Special Populations

Guide · Tier 2

Bacterial Meningitis: Organisms by Age, Diagnosis, and Empiric Treatment

Guide · Tier 2

Infective Endocarditis: Duke Criteria, Common Organisms, and Antibiotic Therapy

Guide · Tier 2

HIV Pathophysiology and Staging

HIV (Human Immunodeficiency Virus, RNA retrovirus) infects CD4+ T cells, macrophages, and dendritic cells via CCR5/CXCR4 co-receptors. Viral replication depletes CD4 T cells over years → immunodeficiency. Stages: Acute HIV (seroconversion illness): 2–4 weeks post-exposure — fever, rash, lymphadenopathy, pharyngitis, myalgias ('mononucleosis-like syndrome'); p24 antigen rises before antibodies (4th generation antigen/antibody test detects both). Chronic/Asymptomatic HIV: years; viral replication continues, CD4 slowly declining. AIDS: CD4 <200 OR AIDS-defining illness/condition. Diagnosis: 4th generation HIV Ag/Ab combination test (initial); reactive screen confirmed with HIV-1/HIV-2 differentiation assay. Viral load (HIV RNA PCR): measures disease activity; used to monitor ART response. Goal of ART: viral load undetectable (<20–50 copies/mL).

CD4 Thresholds for OI Risk

CD4 <500: HIV itself; oral hairy leukoplakia (EBV), thrush (Candida), recurrent bacterial infections. CD4 <200: Pneumocystis jirovecii pneumonia (PCP) — start TMP-SMX prophylaxis. CD4 <100: Toxoplasma gondii encephalitis (ring-enhancing lesions, serology positive, multiple lesions) — start TMP-SMX (also covers Toxo). Cryptococcus neoformans meningitis (India ink, cryptococcal antigen) — fluconazole prophylaxis if CD4 <100. CD4 <50: Mycobacterium avium complex (MAC/MAI) — disseminated disease with fever, night sweats, weight loss, hepatosplenomegaly, elevated ALP — azithromycin weekly prophylaxis. CMV retinitis (visual symptoms, 'pizza pie' fundoscopy) — ganciclovir treatment. Memory: 200=PCP; 100=Toxo+Crypto; 50=MAC+CMV.

ART Regimens and IRIS

When to start ART: ALL HIV-positive patients, regardless of CD4 count or viral load. Preferred regimen: 2 NRTIs + 1 integrase inhibitor (INSTI). Specific: tenofovir/emtricitabine (backbone) + bictegravir (Biktarvy) or dolutegravir (Triumeq). Mechanisms: NRTIs (nucleoside reverse transcriptase inhibitors) — chain terminators, incorporate into viral DNA and block elongation. NNRTIs (non-nucleoside RTIs) — allosteric inhibitors of reverse transcriptase (efavirenz, rilpivirine). Protease inhibitors (PIs) — prevent viral maturation (ritonavir, darunavir); boosted with cobicistat or ritonavir (inhibit CYP3A4 to increase PI levels). INSTIs — prevent HIV DNA integration into host genome (dolutegravir, bictegravir, raltegravir). Entry inhibitors: maraviroc (CCR5 antagonist — use only if CCR5-tropic HIV), enfuvirtide (T-20, fusion inhibitor). IRIS (Immune Reconstitution Inflammatory Syndrome): paradoxical worsening of OI as immune system recovers on ART. Most common with TB, Cryptococcus, CMV. Treat by continuing ART + corticosteroids for severe IRIS.

Test yourself

Quick check — 2 questions

1. A 32-year-old HIV+ patient has CD4 count of 85. What prophylactic medications should he be receiving?

2. An HIV patient on ART for 3 months develops fever, worsening cervical lymphadenopathy, and new pulmonary infiltrates. CD4 has risen from 50 to 200. The most likely explanation is:

Frequently asked questions

How do you distinguish Toxoplasma encephalitis from CNS lymphoma in AIDS?

Both cause ring-enhancing CNS lesions in AIDS (CD4 <100). Distinguishing features: Toxoplasma: multiple lesions (typically), positive Toxoplasma IgG serology in >95% of cases, lesions at basal ganglia/corticomedullary junction, fever common. CNS lymphoma (primary): usually solitary lesion, EBV-positive (CSF EBV PCR positive in ~90%), positive FDG-PET on lesion ('hot'). In clinical practice: try empiric toxoplasmosis treatment (pyrimethamine + sulfadiazine + leucovorin) for 2 weeks — if response (lesions shrink), confirm Toxo. If no response or serology negative → brain biopsy.

What is the HIV transmission risk for healthcare workers after needlestick?

Average risk of HIV transmission after a single needlestick from HIV-positive source is ~0.3%. Risk increases with: large-gauge hollow bore needle, visible blood on device, deep puncture, source with high viral load. Post-exposure prophylaxis (PEP): start within 72 hours (ideally <2 hours) — preferred regimen is tenofovir/emtricitabine + raltegravir × 28 days. Risk per unprotected sexual exposure: receptive anal intercourse ~1.4%; insertive anal 0.08%; receptive vaginal 0.08%; insertive vaginal 0.04%. PrEP (pre-exposure prophylaxis): tenofovir/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy) for high-risk individuals — reduces transmission risk by >99% with adherence.

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