What post-exposure prophylaxis (PEP) regimen is recommended for a patient with impaired liver function?

HIV Post-Exposure Prophylaxis in Patients with Altered Liver Function

In patients with impaired liver function requiring HIV post-exposure prophylaxis, use the preferred regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days, initiated immediately within 72 hours of exposure, with close monitoring for hepatotoxicity. 1, 2, 3

Immediate Initiation Protocol

• Start PEP immediately upon presentation without delay, regardless of liver function test results, pending assessments, or specialist consultation 1, 2
• Efficacy decreases dramatically with each passing hour; the 72-hour window is an absolute maximum 1, 2
• Perform baseline liver function tests (AST, ALT, bilirubin) after initiating the first dose, not before 1, 3

Preferred Regimen for Liver Impairment

The optimal choice is BIC/FTC/TAF (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg) once daily for exactly 28 days 1, 2, 3

Advantages in Liver Disease:

• Tenofovir alafenamide (TAF) has superior safety profiles compared to older formulations and is preferred even in patients with hepatic concerns 1, 3
• Single-tablet regimen improves completion rates, which is critical in patients who may experience medication intolerance 3
• Well-tolerated with minimal gastrointestinal side effects (nausea 15.4%, fatigue 9.6%) compared to older PEP regimens 4
• No dose adjustment required for mild to moderate hepatic impairment 5

Alternative Regimen

If BIC/FTC/TAF is unavailable, use dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days 1, 2, 3

Critical Monitoring in Liver Disease

Baseline Assessment (after first dose):

• Hepatitis B surface antigen (HBsAg) - critical as discontinuation of tenofovir-containing regimens can cause severe hepatitis B exacerbation 5
• AST, ALT, total and direct bilirubin 6
• Complete blood count and renal function 1, 3
• Review all concurrent medications for potential drug interactions that could worsen hepatotoxicity 7, 8

Enhanced Monitoring Schedule for Liver Impairment:

• Within 72 hours: clinical evaluation and liver function tests 1, 3
• Every 2 weeks during the 28-day course (more frequent than standard monitoring) 9
• Immediate evaluation if clinical symptoms develop (jaundice, right upper quadrant pain, dark urine, clay-colored stools) 7, 9

Regimens to AVOID in Liver Disease

Never use nevirapine (NVP) in patients with any degree of liver impairment - it has been associated with severe hepatotoxicity including liver failure requiring transplantation in an exposed person taking PEP 6

Avoid if possible:

• Ritonavir-boosted regimens (difficult to take, poorly tolerated, many drug interactions that can worsen hepatotoxicity) 6
• Didanosine (ddI) + stavudine (d4T) combinations (associated with pancreatitis, lactic acidosis, and hepatitis) 6

Management of Hepatotoxicity During PEP

Minor elevations (AST/ALT < 5 times upper limit of normal):

• Continue PEP with increased monitoring every 1-2 weeks 9
• Exclude hypersensitivity reactions 9
• Provide supportive care with anti-emetics if needed 3

Severe hepatotoxicity indicators (any of the following):

• AST/ALT ≥ 5 times upper limit of normal with symptoms 9
• Coagulopathy (elevated INR/PT) 10, 9
• Elevated ammonia levels 9
• Clinical jaundice or hepatic encephalopathy 10, 7

Action: Immediately discontinue all antiretroviral therapy and seek expert consultation via the National Clinicians' Post-Exposure Prophylaxis Hotline at 1-888-448-4911 1

Critical Duration Requirement

The full 28-day course must be completed regardless of liver enzyme fluctuations or subsequent source patient information, unless severe hepatotoxicity develops 1, 2, 3

• Incomplete adherence significantly reduces PEP effectiveness 1, 3
• No option for early discontinuation based on improved liver function tests 3

Special Considerations for Hepatitis B Coinfection

If HBsAg positive: The tenofovir-containing regimen provides dual benefit for both HIV PEP and hepatitis B treatment 5

Critical warning: Severe acute exacerbation of hepatitis B can occur after discontinuation of tenofovir-containing regimens; monitor liver function closely for several months after completing the 28-day PEP course 5

Follow-Up Testing Schedule

• 4-6 weeks post-exposure: HIV antigen/antibody test plus nucleic acid test (NAT), liver function tests 1, 2, 3
• 12 weeks post-exposure: HIV antigen/antibody combination immunoassay and NAT, liver function tests 1, 2, 3
• Immediate testing if acute retroviral symptoms or hepatic symptoms develop 1, 3

Common Pitfalls to Avoid

• Never delay PEP initiation to obtain baseline liver function tests or await specialist consultation 1, 2, 3
• Never use older regimens (zidovudine-based) when modern single-tablet options are available, as they have higher rates of side effects and lower completion rates 6, 1
• Never discontinue PEP early based on improved liver enzymes unless severe hepatotoxicity develops 1, 3
• Never fail to screen for hepatitis B before starting tenofovir-containing regimens due to risk of severe exacerbation upon discontinuation 5
• Never use two-drug regimens unless three-drug options are absolutely unavailable 1, 3