A 32-year-old man with newly diagnosed HIV-1 infection (CD4 count 180 cells/μL, viral load 150,000 copies/mL) presents to the antiretroviral clinic. He has no prior opportunistic infections. Physical examination reveals oral candidiasis and mild hepatosplenomegaly. Baseline investigations show: ALT 45 U/L, creatinine 0.9 mg/dL, HBsAg negative, HCV antibody negative. The patient is counselled on adherence and started on a first-line regimen. After 2 weeks, he develops severe rash, fever, and facial edema. Which antiretroviral agent is most likely responsible for this adverse reaction?

Explanation

## Clinical Presentation Analysis The patient presents with **severe cutaneous and systemic hypersensitivity reaction** (rash, fever, facial edema) occurring 2 weeks after initiating antiretroviral therapy. This timing and symptom cluster are pathognomonic for nevirapine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) or Stevens-Johnson syndrome (SJS). ## Nevirapine Hypersensitivity Syndrome **Key Point:** Nevirapine causes the most severe and frequent hypersensitivity reactions among NNRTIs, occurring in 15–20% of patients, with 0.3% progressing to fatal hepatotoxicity or SJS. **High-Yield:** Risk factors for nevirapine hypersensitivity include: - CD4 count >250 cells/μL in women (this patient is male with CD4 180, lower risk but still susceptible) - Female sex - HLA-B*3505 allele (Southeast Asian ancestry) - Concurrent hepatitis B or C co-infection (not present here) **Clinical Pearl:** Nevirapine reactions typically manifest in the first 2–6 weeks of therapy with: - Maculopapular rash (often involving face, trunk, palms, soles) - Fever, facial/laryngeal edema - Hepatitis (elevated transaminases) - Eosinophilia - Lymphadenopathy ## Management 1. **Immediate:** Discontinue nevirapine and all other suspected agents 2. **Monitoring:** Check CBC (eosinophilia), LFTs (hepatitis), skin biopsy if SJS suspected 3. **Supportive care:** Antihistamines, corticosteroids for severe cutaneous reactions 4. **Alternative regimen:** Switch to efavirenz-based or integrase inhibitor-based therapy ## Comparison with Other Agents | Agent | Hypersensitivity Profile | Timing | Severity | |-------|--------------------------|--------|----------| | **Nevirapine** | 15–20% incidence | 2–6 weeks | Severe (SJS, DRESS, hepatitis) | | **Efavirenz** | Rare cutaneous reactions | Variable | Mild rash, usually self-limited | | **Tenofovir** | No hypersensitivity syndrome | N/A | Renal toxicity (chronic), not acute | | **Ritonavir** | Rare hypersensitivity | Variable | Mild rash, GI upset | **Warning:** Do NOT rechallenge with nevirapine once hypersensitivity occurs — risk of fatal reaction is high. [cite:Harrison 21e Ch 197]