How often should liver enzymes be monitored in individuals with Human Immunodeficiency Virus (HIV) on Antiretroviral Therapy (ART)?

Liver Enzyme Monitoring in HIV Patients on ART

For clinically stable HIV patients on antiretroviral therapy with viral suppression, liver enzyme monitoring should be performed every 6 months during the first year, then can be reduced to annually after 5 years of stable suppression, with more frequent monitoring (every 2 weeks to monthly) only during the first 12 weeks if using nevirapine or in patients with hepatitis coinfection. 1

Initial Monitoring Strategy

Before Starting ART

• Baseline liver function tests (including AST, ALT, and bilirubin) should be obtained to characterize general health before initiating therapy 1
• Screen for viral hepatitis A, B, and C coinfection, as these significantly increase hepatotoxicity risk 1
• These baseline results should not delay ART initiation unless there is preexisting severe liver damage 1

Early Treatment Phase (First 6 Months)

• Standard regimens: Evaluate for medication toxicity at every clinical encounter during the first 6 months 1
• Nevirapine-containing regimens: Monitor liver enzymes every 2 weeks for the first month, then monthly for the first 12 weeks, then every 1-3 months thereafter due to the 12.5% incidence of hepatotoxicity and risk of fulminant hepatic failure 1
• Most hepatotoxicity (>80%) occurs within the first 3 months of ART initiation and is typically asymptomatic 2

Long-Term Monitoring Schedule

After Achieving Viral Suppression

• First year of viral suppression: Monitor safety laboratories including liver enzymes every 6 months 1
• After 1-5 years of stable suppression: Continue monitoring every 6 months 1
• After >5 years of stable suppression: Can reduce to annual monitoring if the patient prefers less frequent testing and remains clinically stable, virologically suppressed, and adherent 1

Special Populations Requiring Intensified Monitoring

Hepatitis C coinfection: This is the single most important risk factor for severe hepatotoxicity, with a 2.7-fold increased risk 3. These patients should have liver enzymes monitored more frequently, particularly when initiating ART with CD4 counts <200 cells/μL, as immune reconstitution can trigger hepatitis exacerbation 4

Hepatitis B coinfection: Also increases hepatotoxicity risk and warrants closer monitoring 1, 3

Other high-risk factors requiring closer monitoring 3:

• Baseline elevated liver enzymes (strongest predictor across all regimens)
• Concomitant hepatotoxic medications
• Thrombocytopenia
• Renal insufficiency
• Alcohol abuse 1

Regimen-Specific Considerations

Protease Inhibitor (PI) Regimens

• PI-associated hepatotoxicity can occur at any time during treatment, not just early 1
• Ritonavir-containing regimens have higher rates of severe hepatotoxicity compared to other PIs 1
• Continue regular 6-month monitoring throughout treatment duration

Integrase Inhibitor Regimens (e.g., Dolutegravir)

• These have superior hepatic safety profiles compared to NNRTIs and PIs 5
• Standard monitoring intervals apply (every 6 months, then annually after 5 years) 1

Injectable Cabotegravir PrEP

• Liver enzyme testing every 6 months is specifically recommended 1

Clinical Response to Abnormal Results

Definition of Severe Hepatotoxicity

• AST or ALT >5 times upper limit of normal (ULN) 3, 4
• Total bilirubin >2.5 times ULN 3

Management Algorithm

• Asymptomatic mild elevations (3-5x ULN): Many resolve spontaneously without therapy modification 1
• Symptomatic or severe elevations: Assess for clinical hepatitis symptoms (jaundice, hepatomegaly, GI symptoms) and consider ART modification or interruption 1
• Patients with CD4 <200 cells/μL and hepatitis coinfection: Highest risk for liver failure; consider prophylactic hepatitis treatment 4

Critical Pitfalls to Avoid

• Do not delay ART initiation while waiting for baseline liver function results unless severe preexisting liver disease is evident 1
• Do not routinely withhold HAART from hepatitis-coinfected patients, but monitor closely for immune reconstitution hepatitis 1
• Do not ignore asymptomatic elevations in the first 3 months, as most hepatotoxicity occurs early and without symptoms 2
• Do not use the same monitoring schedule for nevirapine as for other regimens—it requires intensive early monitoring due to risk of fulminant hepatic necrosis 1