What are the considerations for using Biltarvy (bictegravir, emtricitabine, tenofovir alafenamide) in patients with liver failure?

Biltarvy Use in Liver Failure

Biltarvy is not recommended in patients with severe hepatic impairment (Child-Pugh C), but no dose adjustment is required for mild to moderate hepatic impairment (Child-Pugh A or B). 1

Dosing Recommendations by Severity of Liver Disease

Mild to Moderate Hepatic Impairment (Child-Pugh A or B)

• No dose adjustment is required for Biltarvy in patients with compensated cirrhosis or mild-to-moderate hepatic impairment 2, 1
• Standard dosing: One tablet containing 50 mg bictegravir, 200 mg emtricitabine, and 25 mg tenofovir alafenamide once daily 1
• The integrase inhibitor component (bictegravir) and nucleoside analogs (tenofovir, emtricitabine) do not require dose adjustment in this population 2

Severe Hepatic Impairment (Child-Pugh C)

• Biltarvy is not recommended in patients with severe hepatic impairment 1
• Integrase strand transfer inhibitors (InSTIs) like bictegravir should be used with caution in Child-Pugh C disease, though no specific dose adjustment guidelines exist 2
• The lack of pharmacokinetic data in severe hepatic dysfunction and reduced hepatic cytochrome enzyme activity create unpredictable drug metabolism 2, 3

Critical Monitoring Requirements

Before Initiating Biltarvy

• Test for hepatitis B virus (HBV) infection prior to or when initiating therapy 1
• This is essential because severe acute exacerbations of hepatitis B can occur upon discontinuation in HBV/HIV coinfected patients 1
• Assess baseline serum creatinine, estimated creatinine clearance, urine glucose, and urine protein 1

During Treatment

• Closely monitor hepatic function in patients coinfected with HIV-1 and HBV throughout treatment 1
• Monitor for signs of hepatic decompensation, particularly in the first 3-6 months when clinical deterioration can occur despite antiviral therapy 2
• Assess renal function periodically, as tenofovir alafenamide can be used when creatinine clearance is above 30 mL/min 2

Special Considerations for Decompensated Cirrhosis

Hepatitis B Coinfection Context

• In patients with decompensated HBV-related cirrhosis, tenofovir plus emtricitabine (components of Biltarvy) achieved 87.8% undetectable HBV DNA at week 48 2
• However, these data were generated in HBV monoinfection, not HIV/HBV coinfection with severe hepatic impairment 2

Risk of Hepatic Decompensation Upon Discontinuation

• Severe acute exacerbations of hepatitis B have been reported in HIV-1/HBV coinfected patients who discontinued emtricitabine and/or tenofovir-containing products 1
• If Biltarvy must be discontinued in HBV coinfected patients, anti-hepatitis B therapy may be warranted 1

Practical Algorithm for Prescribing Biltarvy in Liver Disease

Step 1: Assess Severity of Hepatic Impairment

• Child-Pugh A or B → Proceed with standard dosing 2, 1
• Child-Pugh C → Do not use Biltarvy; consider alternative regimens 1

Step 2: Screen for Hepatitis B Coinfection

• If HBV coinfected → Counsel patient about risk of severe hepatitis flare upon discontinuation 1
• Ensure close hepatic function monitoring is feasible 1

Step 3: Evaluate Renal Function

• Estimated creatinine clearance ≥30 mL/min → Safe to use tenofovir alafenamide component 2, 1
• Estimated creatinine clearance 15 to <30 mL/min → Biltarvy not recommended 1
• Estimated creatinine clearance <15 mL/min without chronic hemodialysis → Biltarvy not recommended 1

Step 4: Assess Drug-Drug Interactions

• Do not coadminister with rifampin (contraindicated) 1
• Do not coadminister with dofetilide (contraindicated) 1
• Biltarvy has minimal drug-drug interactions with hepatitis C direct-acting antivirals, making it suitable for HIV/HCV coinfection 2

Common Pitfalls and How to Avoid Them

Pitfall 1: Using Biltarvy in Child-Pugh C Cirrhosis

• The FDA label explicitly states Biltarvy is not recommended in severe hepatic impairment 1
• Alternative options include individual dose-adjusted components or regimens with more data in advanced liver disease 2

Pitfall 2: Failing to Test for Hepatitis B Before Initiation

• This creates risk of unrecognized HBV flare upon discontinuation 1
• Always test HBsAg and anti-HBc before starting therapy 1

Pitfall 3: Ignoring Renal Function in Cirrhotic Patients

• Cirrhotic patients frequently have hepatorenal syndrome or chronic kidney disease 2
• Tenofovir alafenamide requires creatinine clearance ≥30 mL/min for safe use 2, 1

Pitfall 4: Assuming All InSTI-Based Regimens Are Equivalent in Liver Disease

• While bictegravir, dolutegravir, and raltegravir do not require dose adjustment in mild-to-moderate impairment, none are recommended in Child-Pugh C 2
• Tenofovir, lamivudine, raltegravir, and rilpivirine are the only antiretrovirals that do not require dose adjustment even in severe hepatic impairment 2, 4

Alternative Antiretroviral Options When Biltarvy Is Contraindicated

For Severe Hepatic Impairment (Child-Pugh C)

• Raltegravir plus lamivudine (both require no dose adjustment in severe hepatic impairment) 2, 4
• Rilpivirine-based regimens (no dose adjustment required) 2, 4
• Avoid protease inhibitors, which cause more severe hepatotoxicity and require dose adjustment 2, 4

For Patients with Hepatotoxicity Concerns

• Avoid nevirapine, which has the highest risk of severe hepatotoxicity and is contraindicated in liver dysfunction 4
• Protease inhibitors (especially ritonavir-boosted regimens) cause more hepatotoxicity than InSTIs 4

Monitoring for Adverse Events

Hepatic Monitoring

• Monitor liver enzymes at baseline and periodically during treatment 5
• In HBV coinfected patients, monitor HBV DNA levels and liver function every 3 months 2

Renal Monitoring

• Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein at baseline and during treatment 1
• In patients with chronic kidney disease, also assess serum phosphorus 1

Common Adverse Events

• Most common adverse reactions (≥5%): diarrhea, nausea, and headache 1
• These are generally mild and do not require discontinuation 6