Does Biktarvy Increase Bilirubin?
Yes, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) causes bilirubin elevations in approximately 17% of patients, primarily mild Grade 1 increases (1.0-1.5 × ULN), which are benign and do not represent liver toxicity. 1
Mechanism of Bilirubin Elevation
- Bictegravir inhibits bilirubin transporters (OATP1B1 and OATP1B3), similar to other integrase inhibitors, leading to unconjugated (indirect) hyperbilirubinemia without affecting actual liver function 2
- This mechanism is distinct from hepatocellular injury and does not involve ALT elevations, making it clinically distinguishable from true liver damage 3, 2
- The hyperbilirubinemia manifests as isolated unconjugated increases without transaminase elevation, which is the hallmark of transporter inhibition rather than hepatotoxicity 2
Clinical Trial Data
- In pivotal trials (1489 and 1490) through Week 144, total bilirubin increases occurred in 17% of Biktarvy-treated patients: 12% Grade 1 (1.0-1.5 × ULN) and 4% Grade 2 (1.5-2.5 × ULN) 1
- This compares to only 7-8% in comparator groups (ABC/DTG/3TC and DTG+FTC/TAF), suggesting bictegravir contributes to the bilirubin elevation 1
- No treatment discontinuations occurred due to hepatic adverse events through Week 144, confirming the benign nature of these elevations 1
- At 96 weeks, Biktarvy demonstrated sustained efficacy with 84% achieving HIV RNA <50 copies/mL, with continued good tolerability 4
Clinical Significance and Management
- These bilirubin elevations are clinically benign and do not require treatment discontinuation 2, 1
- The increases are not associated with hepatotoxicity or liver dysfunction, as evidenced by the absence of concurrent ALT elevations 3, 2
- Patients with Gilbert's syndrome may experience more pronounced unconjugated hyperbilirubinemia when taking medications that inhibit UDP glucuronyl transferase, though this is more characteristic of nilotinib than bictegravir 5
Monitoring Recommendations
- Baseline liver function tests including total and direct bilirubin should be obtained before initiating Biktarvy 1
- If bilirubin elevation occurs, determine whether it is predominantly unconjugated (indirect) or conjugated (direct) to distinguish transporter inhibition from hepatocellular injury 6, 2
- Isolated unconjugated hyperbilirubinemia without ALT elevation does not require drug discontinuation and represents the expected pharmacologic effect of bictegravir 2
- Monitor for concurrent ALT elevations, which would suggest true hepatotoxicity rather than benign transporter inhibition 3
Special Populations
HIV/HBV Coinfection
- In HIV/HBV coinfected patients switched to Biktarvy, 89% achieved HIV suppression and 86% achieved HBV suppression at Week 24 with no hepatitis flares observed 7
- No serious adverse events or treatment discontinuations occurred in this coinfected population, supporting safety in patients with underlying liver disease 7
Hepatic Impairment
- Tenofovir alafenamide (TAF component) is safe in mild hepatic impairment but not currently recommended in moderate-severe impairment (Child-Pugh B or C) 8
Key Clinical Pitfalls to Avoid
- Do not confuse bictegravir-induced unconjugated hyperbilirubinemia with hepatotoxicity—the absence of ALT elevation is the critical distinguishing feature 3, 2
- Do not discontinue Biktarvy for isolated Grade 1-2 bilirubin elevations without evidence of hepatocellular injury 1
- Do not attribute all bilirubin increases to Biktarvy in coinfected patients—consider hemolysis from ribavirin if used for HCV treatment, or other hepatotoxic medications 5, 6
- In patients with cirrhosis, greater frequency of bilirubin increases may occur, but this still represents transporter inhibition rather than worsening liver disease 5, 3