CD4 < 200 Prophylaxis
Pneumocystis jirovecii (PJP): TMP-SMX 1 DS daily (dapsone or atovaquone if sulfa allergy). Discontinue when CD4 > 200 for 3+ months.
CD4 < 100 Prophylaxis
Toxoplasma gondii (if IgG seropositive): TMP-SMX 1 DS daily. Cryptococcal antigen screening if symptomatic headache/fever.
CD4 < 50 Protocol
Mycobacterium avium complex (MAC): Azithromycin 1200 mg weekly (only if not on fully suppressive ART). Screen for CMV retinitis (funduscopic exam).
First-Line ART Regimen
Integrase Strand Transfer Inhibitor (INSTI) + 2 NRTIs: Bictegravir/TAF/FTC (Biktarvy) or Dolutegravir + Abacavir/Lamivudine (test HLA-B*5701 first).
Opportunistic Infections by CD4 Nadir & Management Guidelines
| CD4 Cell Count Threshold | Opportunistic Pathogen & Disease | Classic Clinical Presentation & Diagnostics | First-Line Treatment & Prophylaxis |
|---|---|---|---|
| CD4 < 200 / μL | Pneumocystis jirovecii (PJP) | Subacute exertional dyspnea, dry cough, hypoxemia disproportionate to exam; bilateral perihilar ground-glass infiltrates; ↑ LDH | High-dose TMP-SMX (IV/PO) × 21 days; add prednisone if PaO2 < 70 mmHg or A-a gradient ≥ 35; Prophylaxis: TMP-SMX 1 DS daily |
| CD4 < 100 / μL | Toxoplasma gondii | Headache, focal neurologic deficits, seizures; Brain MRI: multiple ring-enhancing lesions with surrounding vasogenic edema in basal ganglia | Sulfadiazine + Pyrimethamine + Leucovorin; Prophylaxis: TMP-SMX 1 DS daily (covers both PJP and Toxoplasma) |
| CD4 < 100 / μL | Cryptococcus neoformans | Subacute meningoencephalitis, fever, elevated ICP; India ink / cryptococcal antigen (CrAg) in CSF; Sabouraud agar growth | Induction: Liposomal Amphotericin B + Flucytosine × ≥ 2 weeks → Consolidation: Fluconazole; serial lumbar punctures to relieve ICP |
| CD4 < 50 / μL | Mycobacterium avium complex (MAC) | Fever, night sweats, severe weight loss, chronic watery diarrhea, hepatosplenomegaly; elevated alkaline phosphatase; acid-fast bacilli on blood culture | Clarithromycin + Ethambutol ± Rifabutin; Primary prophylaxis: Azithromycin 1200 mg weekly (only if suppressive ART delayed) |
| CD4 < 50 / μL | Cytomegalovirus (CMV) Retinitis | Painless visual blurring, floaters, scotomas; Funduscopy: 'ketchup and cottage cheese' (perivascular retinal hemorrhages + white necrotic exudates) | IV Ganciclovir / Valganciclovir or intravitreal Foscarnet; routine ophthalmologic monitoring to avoid permanent blindness |
Antiretroviral Pharmacology & Key Board Toxicities
| Drug Class | Representative Agents | Mechanism of Action | High-Yield Board Toxicity / Contraindication |
|---|---|---|---|
| NRTIs (Nucleoside Reverse Transcriptase Inhibitors) | Tenofovir (TDF vs TAF), Emtricitabine, Abacavir, Lamivudine, Zidovudine | Competitively inhibit reverse transcriptase; lack 3'-OH group causing chain termination | Abacavir: Fatal hypersensitivity in HLA-B*5701 positive; TDF: Fanconi nephropathy and bone demineralization (TAF has less renal/bone toxicity); Zidovudine: Macrocytic anemia and bone marrow suppression |
| NNRTIs (Non-Nucleoside) | Efavirenz, Rilpivirine, Nevirapine | Allosterically bind reverse transcriptase near active site; do not require phosphorylation | Efavirenz: Vivid nightmares, neuro-psychiatric disturbances, teratogenicity (neural tube defects); Nevirapine: Fulminant hepatotoxicity, SJS/TEN |
| INSTIs (Integrase Inhibitors) | Bictegravir, Dolutegravir, Raltegravir | Inhibit HIV integrase, blocking proviral DNA integration into host cellular chromosome | Dolutegravir / Bictegravir: Weight gain, insomnia; Raltegravir: Rhabdomyolysis and ↑ CK. Modern first-line backbone due to high resistance barrier |
| Protease Inhibitors (PIs) | Darunavir, Atazanavir, Ritonavir (booster) | Prevent cleavage of Gag-Pol polyprotein, producing immature, non-infectious virions | Metabolic syndrome: Hyperlipidemia, insulin resistance/lipodystrophy; Atazanavir: Indirect hyperbilirubinemia, nephrolithiasis; Ritonavir: Potent CYP3A4 inhibitor |
OMM Board Correlate: Immune System Drainage & Thoracic Duct
- Lymphatic Decongestion Protocol: In chronic viral infections and generalized lymphadenopathy, lymphatic drainage order is mandatory: 1. Release thoracic inlet (clavicle, 1st rib, T1), 2. Treat thoracoabdominal diaphragm (L1–L3 crura), 3. Pelvic diaphragm, 4. Apply gentle thoracic and pedal pumps.
- Splenic Pump Caution: While gentle thoracic pump enhances immunoglobulin circulation, vigorous splenic pump is strictly avoided if splenomegaly is present due to risk of subcapsular splenic rupture.
Board Traps & Common Distractors
- In patients presenting with Cryptococcal meningitis, NEVER start Antiretroviral Therapy (ART) immediately; initiating ART prior to clearing CSF infection triggers lethal Immune Reconstitution Inflammatory Syndrome (IRIS) with cerebral herniation. Delay ART by 2–4 weeks until fungal burden drops.
- Primary CNS Lymphoma (PCNSL) in HIV is caused by EBV and presents as a solitary periventricular ring-enhancing lesion with positive CSF EBV PCR, distinguishing it from multifocal Toxoplasmosis.
- Abacavir must NEVER be rechallenged if hypersensitivity occurs; repeat administration triggers fatal anaphylactic circulatory collapse.