Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia

Détails

ID Serval
serval:BIB_50D5FB6BE899
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia
Périodique
Journal of Infectious Diseases
Auteur(s)
Rotger  M., Taffe  P., Bleiber  G., Gunthard  H. F., Furrer  H., Vernazza  P., Drechsler  H., Bernasconi  E., Rickenbach  M., Telenti  A.
ISSN
0022-1899 (Print)
Statut éditorial
Publié
Date de publication
10/2005
Volume
192
Numéro
8
Pages
1381-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct 15
Résumé
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.
Mots-clé
Adult Antiretroviral Therapy, Highly Active/*adverse effects Cohort Studies Female Gilbert Disease/*complications Glucuronosyltransferase/*genetics Humans Hyperbilirubinemia/*chemically induced/complications Male Middle Aged Treatment Outcome
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/01/2008 9:52
Dernière modification de la notice
08/05/2019 18:32
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