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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: An observational cohort study
Journal of Infectious Diseases, Volume 203, No. 2, Year 2011
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Description
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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Ledergerber, Bruno
Switzerland, Zurich
Universität Zürich
Cavassini, Matthias L.
Switzerland, Lausanne
Université de Lausanne Unil
Hirschel, B. J.
Switzerland, Geneva
University Hospital
Bernasconi, Enos
Unknown Affiliation
Elzi, Luigia
Switzerland, Basel
Universitätsspital Basel
Vernazza, Pietro Luigi
Switzerland, St Gallen
Kantonsspital St.gallen
Furrer, Hansjakob Jackob
Switzerland, Bern
University Hospital Bern
Günthard, Hüldrych Fritz
Switzerland, Zurich
Universität Zürich
Telenti, Amalio
Switzerland, Lausanne
Université de Lausanne Unil
Battegay, Manuel
Unknown Affiliation
Bernasconi, Enos
Unknown Affiliation
Böni, Jürg
Unknown Affiliation
Bucher, Heíner C.C.
Unknown Affiliation
Bürgisser, Ph
Unknown Affiliation
Calmy, Alexandra L.
Unknown Affiliation
Cattacin, Sandro
Unknown Affiliation
Cavassini, Matthias
Unknown Affiliation
Dubs, Rolf W.
Unknown Affiliation
Egger, Matthias
Unknown Affiliation
Fischer, Marek
Unknown Affiliation
Flepp, Markus J.
Unknown Affiliation
Fontana, Adriano
Unknown Affiliation
Francioli, Patrick B.
Unknown Affiliation
Furrer, Hansjakob
Unknown Affiliation
Fux, Christoph Andreas
Unknown Affiliation
Gorgievski, Meri
Unknown Affiliation
Günthard, Huldrych F.
Unknown Affiliation
Hirsch, Hans H.
Unknown Affiliation
Hirschel, B.
Unknown Affiliation
Hösli, Irene Mathilde
Unknown Affiliation
Kahlert, Christian R.
Unknown Affiliation
Kaiser, Laurent K.
Unknown Affiliation
Karrer, Urs
Unknown Affiliation
Kind, Christian H.
Unknown Affiliation
Klimkait, Thomas
Unknown Affiliation
Martinetti, Gladys
Unknown Affiliation
Müller, Nicolas J.
Unknown Affiliation
Nadal, David
Unknown Affiliation
Paccaud, Fred Michel
Unknown Affiliation
Pantaleo, Giuseppe P.
Unknown Affiliation
Rauch, Andri
Unknown Affiliation
Regenass, Stephan
Unknown Affiliation
Rickenbach, Martin
Unknown Affiliation
Rudin, Christoph
Unknown Affiliation
Schmid, Patrick
Unknown Affiliation
Schültze, Detlev
Unknown Affiliation
Schüpbach, Jörg Rg
Unknown Affiliation
Speck, Roberto F.
Unknown Affiliation
Martínez de Tejada, Begoῆa
Unknown Affiliation
Taffé, Patrick
Unknown Affiliation
Trkola, Alexandra
Unknown Affiliation
Vernazza, Pietro L.
Unknown Affiliation
Weber, Rainer
Unknown Affiliation
Yerly, Sabine T.B.D.
Unknown Affiliation
Statistics
Citations: 107
Authors: 54
Affiliations: 6
Identifiers
Doi:
10.1093/infdis/jiq043
ISSN:
00221899
Research Areas
Environmental
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Study Approach
Quantitative