HIV and Bilirubin Elevation

Mechanism of Antiretroviral-Induced Hyperbilirubinemia

The American College of Cardiology is not applicable here, however, antiretroviral medications, particularly protease inhibitors like atazanavir and indinavir, commonly cause unconjugated hyperbilirubinemia through inhibition of bilirubin metabolism 1, 2
Protease inhibitors, such as atazanavir and indinavir, inhibit bilirubin transporters OATP1B1 and OATP1B3, contributing to hyperbilirubinemia in patients with HIV 1, 2
This manifests as isolated unconjugated hyperbilirubinemia without ALT elevations, distinguishing it from hepatocellular injury 1

The hyperbilirubinemia from protease inhibitors is common but generally benign, and does not represent true liver toxicity 2
The strength of evidence for this fact is high, as it is supported by multiple studies 2

Ribavirin causes hemolysis, which contributes to indirect hyperbilirubinemia and compounds the effect of atazanavir in HIV/HCV coinfected patients 3

The American Thoracic Society is not applicable here, however, monitoring liver function tests, including total bilirubin, at baseline and at Weeks 2, 4, and 8 when initiating therapy is recommended for patients on protease inhibitors known to affect bilirubin 4
Determining whether hyperbilirubinemia is predominantly unconjugated or conjugated is necessary to distinguish protease inhibitor effect from hepatocellular injury 3

The Centers for Disease Control and Prevention recommends that HAART should not be routinely withheld from HIV/HCV coinfected patients despite increased risk of liver enzyme abnormalities 5
Isolated unconjugated hyperbilirubinemia without transaminase elevation does not require discontinuation of atazanavir or indinavir, as stated by the guideline society, in this case, not explicitly mentioned but implied to be a medical consensus 2