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Gilbert Syndrome and the Development of Antiretroviral Therapy–Associated Hyperbilirubinemia


Rotger, Margalida; Taffé, Patrick; Bleiber, Gabriela; Günthard, Huldrych F; Furrer, Hansjakob; Vernazza, Pietro; Drechsler, Henning; Bernasconi, Enos; Rickenbach, Martin; Telenti, Amalio (2005). Gilbert Syndrome and the Development of Antiretroviral Therapy–Associated Hyperbilirubinemia. Journal of Infectious Diseases, 192(8):1381-1386.

Abstract

BackgroundUnconjugated hyperbilirubinemia results from Gilbert syndrome and from antiretroviral therapy (ART) containing protease inhibitors. An understanding of the interaction between genetic predisposition and ART may help to identify individuals at highest risk for developing jaundice MethodsWe quantified the contribution of UGT1A1*28 and ART to hyperbilirubinemia by longitudinally modeling 1386 total bilirubin levels in 96 human immunodeficiency virus (HIV)-infected individuals during a median of 6 years ResultsThe estimated average bilirubin level was 8.8 μmol/L (0.51 mg/dL). Atazanavir increased bilirubin levels by 15 μmol/L (0.87 mg/dL), and indinavir increased bilirubin levels by 8 μmol/L (0.46 mg/dL). Ritonavir, lopinavir, saquinavir, and nelfinavir had no or minimal effect on bilirubin levels. Homozygous UGT1A1*28 increased bilirubin levels by 5.2 μmol/L (0.3 mg/dL). As a consequence, 67% of individuals homozygous for UGT1A1*28 and receiving atazanavir or indinavir had ⩾2 episodes of hyperbilirubinemia in the jaundice range (>43 μmol/L [>2.5 mg/dL]), versus 7% of those with the common allele and not receiving either of those protease inhibitors (P<.001). Efavirenz resulted in decreased bilirubin levels, which is consistent with the induction of UDP-glucuronosyltransferase 1A1 ConclusionsGenotyping for UGT1A1*28 before initiation of ART would identify HIV-infected individuals at risk for hyperbilirubinemia and decrease episodes of jaundice

Abstract

BackgroundUnconjugated hyperbilirubinemia results from Gilbert syndrome and from antiretroviral therapy (ART) containing protease inhibitors. An understanding of the interaction between genetic predisposition and ART may help to identify individuals at highest risk for developing jaundice MethodsWe quantified the contribution of UGT1A1*28 and ART to hyperbilirubinemia by longitudinally modeling 1386 total bilirubin levels in 96 human immunodeficiency virus (HIV)-infected individuals during a median of 6 years ResultsThe estimated average bilirubin level was 8.8 μmol/L (0.51 mg/dL). Atazanavir increased bilirubin levels by 15 μmol/L (0.87 mg/dL), and indinavir increased bilirubin levels by 8 μmol/L (0.46 mg/dL). Ritonavir, lopinavir, saquinavir, and nelfinavir had no or minimal effect on bilirubin levels. Homozygous UGT1A1*28 increased bilirubin levels by 5.2 μmol/L (0.3 mg/dL). As a consequence, 67% of individuals homozygous for UGT1A1*28 and receiving atazanavir or indinavir had ⩾2 episodes of hyperbilirubinemia in the jaundice range (>43 μmol/L [>2.5 mg/dL]), versus 7% of those with the common allele and not receiving either of those protease inhibitors (P<.001). Efavirenz resulted in decreased bilirubin levels, which is consistent with the induction of UDP-glucuronosyltransferase 1A1 ConclusionsGenotyping for UGT1A1*28 before initiation of ART would identify HIV-infected individuals at risk for hyperbilirubinemia and decrease episodes of jaundice

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:15 October 2005
Deposited On:23 Oct 2018 13:07
Last Modified:28 Oct 2018 08:18
Publisher:Oxford University Press
ISSN:0022-1899
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1086/466531
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101086466531 (Library Catalogue)

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