Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.

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Version: author
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It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_A32C59CC88C0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.
Journal
Journal of Infectious Diseases
Author(s)
Lubomirov R., Colombo S., di Iulio J., Ledergerber B., Martinez R., Cavassini M., Hirschel B., Bernasconi E., Elzi L., Vernazza P., Furrer H., Günthard H.F., Telenti A.
Working group(s)
Swiss HIV Cohort Study
Contributor(s)
Battegay M., Bernasconi E., Böni J., Bucher HC., Bürgisser P., Calmy A., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Fux CA., Gorgievski M., Günthard HF., Hirsch HH., Hirschel B., Hösli I., Kahlert C., Kaiser L., Karrer U., Kind C., Klimkait T., Ledergerber B., Martinetti G., Müller N., Nadal D., Paccaud F., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schüpbach J., Speck R., de Tejada BM. , Taffé P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1537-6613 (Electronic)
ISSN-L
0022-1899
Publication state
Published
Issued date
2011
Volume
203
Number
2
Pages
246-257
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
BACKGROUND: Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care.
METHODS: A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models.
RESULTS: During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001).
CONCLUSIONS: Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.
Keywords
Adult, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/adverse effects, Antiretroviral Therapy, Highly Active/adverse effects, Cohort Studies, Female, Genetic Markers, HIV Infections/drug therapy, Humans, Male, Medication Adherence/statistics & numerical data, Middle Aged, Pharmacogenetics
Pubmed
Web of science
Open Access
Yes
Create date
22/03/2011 12:31
Last modification date
25/09/2019 7:10
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