Mechanism of indinavir-induced hyperbilirubinemia

Zucker, Stephen D.; Qin, Xiaofa; Rouster, Susan D.; Yu, Fei; Green, Richard M.; Feinberg, Judith; Sherman, Kenneth E.

doi:10.1016/s0016-5085(08)80220-x

Cited by 42 publications

(53 citation statements)

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“…The cumulative proportions of subjects with this outcome were similar for each group at 1 year of treatment. As described elsewhere [10], there were more patients who had elevated total bilirubin levels in the indinavir treatment arm (9 of 12 patients) than there were in the nonindinavir treatment arm (14 of 54;…”

Section: Resultsmentioning

confidence: 67%

Hepatotoxicity Associated with Antiretroviral Therapy Containing Dual versus Single Protease Inhibitors in Individuals Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus

2002

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To determine the rates of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who discontinued therapy as a result of protease inhibitor (PI)-related hepatotoxicity, a retrospective review was conducted. Baseline CD4 counts, plasma HIV RNA levels, and duration of therapy were comparable between single- and dual-PI-treated subjects and between subjects receiving ritonavir-containing therapy and those receiving ritonavir-sparing therapy. The proportions of patients with elevations in alanine aminotransferase level to > or =5 times the upper limit of normal (19% versus 26%) and hyperbilirubinemia (30% versus 38%) were similar between the dual-PI (n=27) and single-PI treatment groups (n=39), respectively. No difference in these characteristics was observed between ritonavir-containing (n=34) and ritonavir-sparing (n=32) treatment arms. Rates of treatment discontinuation due to hepatotoxicity were similar for single-PI and dual-PI therapy and for ritonavir-containing and ritonavir-sparing regimens. Dual-PI therapy and inclusion of ritonavir do not seem to increase the rates of hepatotoxicity in PI-treated, HIV-HCV coinfected subjects.

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Section: Resultsmentioning

confidence: 67%

Hepatotoxicity Associated with Antiretroviral Therapy Containing Dual versus Single Protease Inhibitors in Individuals Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus

2002

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“…A study of 15 HIV-positive men who were receiving indinavir showed greater mean serum bilirubin increases in those with at least one Gilbert's polymorphism than in other individuals (1.5 mg/dL vs 0.3 mg/dL) [14]. A subsequent analysis involving atazanavir yielded similar findings [15].…”

Section: Abacavir Hypersensitivity Reactionmentioning

confidence: 85%

Human genetic variability and HIV treatment response

Haas

2006

Curr HIV/AIDS Rep

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Access to potent antiretroviral medications greatly reduces morbidity and mortality due to HIV/AIDS, but drug toxicity limits treatment success in many individuals. The field of pharmacogenomics strives to understand the influence of human genetic variants in response to medications. Investigators have begun to identify associations among human genetic variants, predisposition to HIV drug toxicities, and likelihood of virologic response. These include associations among abacavir hypersensitivity reactions, HLA type, and hsp70-hom genotypes, and among CYP2B6 polymorphisms, efavirenz pharmacokinetics, and central nervous system symptoms. Pharmacogenomics also holds great promise to suggest novel targets for drug development. The discovery that a naturally occurring, nonfunctional variant of the HIV receptor gene CCR5 protected against HIV infection encouraged the development of CCR5 antagonists. Through continued translational and applied research, pharmacogenomics will ultimately benefit persons living with HIV worldwide by identifying new therapeutic targets and through individualized drug prescribing that is informed by human genetic testing.

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“…Although liver enzyme elevations may develop with any protease inhibitor, lopinavir/ritonavir, fosamprenavir/ritonavir, and nelfinavir appear to be less hepatotoxic [83] and tipranvir/ritonavir most hepatotoxic [84]. An unconjugated hyperbilirubinemia can occur during atazanavir and indinavir therapy but does not reflect liver damage and is related to the inhibition of the uridine diphosphate glucuronosyl transferase enzyme [85, 86]. Dual protease inhibitor therapy does not increase the rate of hepatotoxicity [87].…”

Section: Impact Of Antiretroviral Therapy On Hcv Infectionmentioning

confidence: 99%