Publication

Association of Pharmacogenetic Markers with Premature Discontinuation of First-line Anti-HIV Therapy: An Observational Cohort Study

Journal Paper/Review - Dec 9, 2010

Units
PubMed
Doi

Citation
Lubomirov R, Telenti A, Günthard H, Furrer H, Vernazza P, Elzi L, Bernasconi E, Hirschel B, Cavassini M, Martinez R, Ledergerber B, di Iulio J, Colombo S, the Swiss HIV Cohort Study. Association of Pharmacogenetic Markers with Premature Discontinuation of First-line Anti-HIV Therapy: An Observational Cohort Study. J Infect Dis 2010; 203:246-257.
Type
Journal Paper/Review (English)
Journal
J Infect Dis 2010; 203
Publication Date
Dec 9, 2010
Issn Electronic
1537-6613
Pages
246-257
Brief description/objective

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.