A 38-year-old woman with HIV-1 infection on a stable ART regimen (dolutegravir + tenofovir/lamivudine for 18 months) presents with a 2-week history of nausea, vomiting, and right upper quadrant pain. Liver function tests show AST 280 U/L, ALT 320 U/L, ALP 180 U/L, and bilirubin 2.8 mg/dL. Viral load is undetectable (< 50 copies/mL) and CD4 count is 680 cells/μL. Hepatitis B and C serology are negative. Abdominal ultrasound is normal. What is the next step in management?

Explanation

## Management of Suspected Drug-Induced Liver Injury in HIV-Treated Patients ### Clinical Context This patient presents with acute hepatitis (elevated transaminases, hyperbilirubinemia) while on stable ART with undetectable viral load and preserved CD4 count. The differential includes: - **Drug-induced liver injury (DILI)** from ART (especially dolutegravir, though rare) - **Acute viral hepatitis** (A, E, or other) - **Immune reconstitution inflammatory syndrome (IRIS)** — less likely given stable CD4 > 500 and long duration on ART - **Other causes** (autoimmune, metabolic) ### Diagnostic Approach **High-Yield:** The next step is NOT to stop all drugs immediately, but to: 1. **Investigate the cause** — hepatitis A serology (HAV IgM), hepatitis E serology, and other DILI markers (acetaminophen level if applicable, eosinophilia) 2. **Assess severity** — INR, albumin, encephalopathy signs (this patient has none) 3. **Identify the culprit drug** — dolutegravir is a known but rare cause of DILI; tenofovir and lamivudine are less commonly implicated ### Management Strategy | Step | Rationale | |---|---| | **Continue ART** (initially) | Abrupt cessation risks viral rebound and immune collapse; viral load is undetectable | | **Hold dolutegravir** | If DILI is suspected, discontinue the most likely culprit while continuing backbone NRTIs | | **Obtain HAV serology** | Acute hepatitis A is common in HIV+ patients and is treatable; vaccination is preventive | | **Monitor LFTs closely** | Repeat in 3–5 days; if worsening, escalate to hepatology | | **Avoid hepatotoxic drugs** | Avoid acetaminophen, NSAIDs, and other hepatotoxins | **Clinical Pearl:** Dolutegravir-associated DILI is rare (< 1% incidence) but well-documented. If LFTs improve after discontinuation, rechallenge is generally not recommended. Switch to an alternative integrase inhibitor (e.g., bictegravir) or PI-based regimen. ### Why Not Discontinue All ART? Abrupt cessation of ART in a virologically suppressed patient: - Risks rapid viral rebound (viral load can rise 100-fold in weeks) - Leads to CD4 decline and opportunistic infection risk - May worsen liver inflammation if hepatitis is viral (immune activation) - Is only indicated if there is evidence of fulminant hepatic failure (INR > 1.5, encephalopathy, severe coagulopathy) This patient has no signs of fulminant failure.