A 32-year-old man with newly diagnosed HIV-1 infection (CD4 count 180 cells/μL, viral load 250,000 copies/mL) presents to the antiretroviral clinic. He has no prior opportunistic infections. He is started on a regimen of tenofovir + lamivudine + efavirenz. After 2 weeks of therapy, he develops severe dizziness, vivid nightmares, and difficulty concentrating at work. His liver function tests are normal. Which of the following is the most appropriate next step in management?

Explanation

## Clinical Scenario Analysis The patient is experiencing neuropsychiatric adverse effects (dizziness, vivid nightmares, impaired concentration) attributable to **efavirenz**, a non-nucleoside reverse transcriptase inhibitor (NNRTI) that crosses the blood–brain barrier readily. ## Efavirenz CNS Toxicity Profile **Key Point:** Efavirenz-induced CNS side effects occur in 40–50% of patients within the first 2 weeks of therapy and are **dose-dependent and time-limited**. **High-Yield:** The majority of patients (70–80%) experience spontaneous resolution of dizziness, nightmares, and concentration difficulties within 2–4 weeks as CNS tolerance develops, even without dose adjustment. ## Management Approach | Feature | Efavirenz CNS Toxicity | Hepatotoxicity | Rash | |---------|------------------------|-----------------|------| | Onset | Days 1–14 | Weeks 2–8 | Weeks 2–6 | | Resolution | 2–4 weeks (spontaneous) | Persistent if severe | May progress | | LFTs | Normal | Elevated | Normal | | Management | Reassurance, continue | Switch NNRTI | Discontinue | **Clinical Pearl:** Timing is critical. Since: - Symptoms are within the expected 2-week window - Liver function is normal (excludes hepatotoxicity) - No rash is mentioned (excludes Stevens–Johnson syndrome) - The patient has severe immunosuppression (CD4 180), switching regimens risks treatment interruption and resistance **The correct approach is to continue the current regimen with patient counseling and reassurance.** Efavirenz can be dosed at bedtime to minimize daytime CNS effects. ## Why Switching Is Premature **Warning:** Switching antiretrovirals in the first 2 weeks of therapy is unnecessary and risks: 1. Treatment interruption in a severely immunocompromised patient (CD4 < 200) 2. Selection of resistant virus if adherence lapses during transition 3. Loss of virological suppression Switching is indicated only if: - CNS symptoms persist or worsen after 4 weeks - Hepatotoxicity develops (elevated transaminases) - Severe rash develops (Stevens–Johnson syndrome) [cite:Harrison 21e Ch 197]