A 32-year-old man with newly diagnosed HIV infection (CD4 count 180 cells/μL, viral load 95,000 copies/mL) presents with fever, cough, and dyspnea. Chest X-ray shows bilateral interstitial infiltrates. PCR for Pneumocystis jirovecii is positive. What is the drug of choice for treatment of PCP in this patient?

Explanation

## First-Line Treatment of PCP in HIV **Key Point:** Trimethoprim-sulfamethoxazole (TMP-SMX) is the gold standard first-line agent for both treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) across all CD4 counts and severity levels. ### Dosing and Efficacy - **High-dose TMP-SMX:** 15–20 mg/kg/day of TMP component in divided doses (IV or oral) - **Response rate:** 75–90% in mild-to-moderate disease - **Advantages:** Superior efficacy, broad spectrum (covers concurrent toxoplasmosis, bacterial infections), cost-effective, oral bioavailability ### Adjunctive Corticosteroids In moderate-to-severe PCP (PaO₂ < 70 mmHg or A-a gradient ≥ 35), add: - **Prednisone:** 40 mg BD × 5 days, then 40 mg daily × 5 days, then 20 mg daily until completion - Reduces mortality by ~50% in severe disease ### Alternative Agents (Second-Line) | Agent | Indication | Limitation | | --- | --- | --- | | Pentamidine IV | TMP-SMX intolerance/allergy | Nephrotoxicity, hypoglycemia, pancreatitis | | Atovaquone | Mild-moderate PCP, intolerance | Lower efficacy (~80%), expensive | | Clindamycin + primaquine | Mild-moderate PCP, alternative | Less effective than TMP-SMX, requires G6PD testing | | Dapsone + TMP | Prophylaxis alternative | Not first-line for treatment | **High-Yield:** TMP-SMX is also the preferred prophylactic agent when CD4 < 200 cells/μL, making it the single most important drug in PCP management. **Clinical Pearl:** Rash and fever during TMP-SMX therapy in HIV patients may represent drug reaction or immune reconstitution inflammatory syndrome (IRIS) — do not automatically discontinue; consider continuation with supportive care if clinically feasible. [cite:Harrison 21e Ch 197]