Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia

Rotger, M; Taffe, P; Bleiber, G; Gunthard, HF; Furrer, H; Vernazza, P; Drechsler, H; Bernasconi, E; Rickenbach, M; Telenti, A; Swiss, HIV Cohort Study (2005). Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. Journal of infectious diseases, 192(8), pp. 1381-6. Cary, N.C.: The University of Chicago Press 10.1086/466531

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BACKGROUND: Unconjugated 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. METHODS: We 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. RESULTS: The estimated average bilirubin level was 8.8 micromol/L (0.51 mg/dL). Atazanavir increased bilirubin levels by 15 mu mol/L (0.87 mg/dL), and indinavir increased bilirubin levels by 8 micromol/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 micromol/L (0.3 mg/dL). As a consequence, 67% of individuals homozygous for UGT1A1*28 and receiving atazanavir or indinavir had > or =2 episodes of hyperbilirubinemia in the jaundice range (>43 micromol/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. CONCLUSIONS: Genotyping for UGT1A1*28 before initiation of ART would identify HIV-infected individuals at risk for hyperbilirubinemia and decrease episodes of jaundice.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Furrer, Hansjakob

ISSN:

0022-1899

ISBN:

16170755

Publisher:

The University of Chicago Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:00

Last Modified:

27 Apr 2018 09:11

Publisher DOI:

10.1086/466531

PubMed ID:

16170755

Web of Science ID:

000232002200011

BORIS DOI:

10.7892/boris.25706

URI:

https://boris.unibe.ch/id/eprint/25706 (FactScience: 60775)

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