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. 2013 Oct 16;8(10):e77691.
doi: 10.1371/journal.pone.0077691. eCollection 2013.

Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study

Viktor von Wyl  1 , Thomas Klimkait, Sabine Yerly, Dunja Nicca, Hansjakob Furrer, Matthias Cavassini, Alexandra Calmy, Enos Bernasconi, Jürg Böni, Vincent Aubert, Huldrych F Günthard, Heiner C Bucher, Tracy R Glass; Swiss HIV Cohort Study
Collaborators, Affiliations

Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study

Viktor von Wyl et al. PLoS One. .

Abstract

Background: Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success.

Methods: Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class.

Results: Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens.

Conclusion: Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.

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Conflict of interest statement

Competing Interests: The Swiss HIV Cohort Study drug resistance database was supported by a research grant from commercial sources - The Union Bank of Switzerland and Gilead Science. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Selection of genotypic drug resistance tests.
Figure 2
Figure 2. Kaplan-Meier curves for the association of adherence on the development of new resistance mutations.
The left column is those on PI/r regimens (N=152) and the right column is those on NNRTI regimens (N=162).
See this image and copyright information in PMC

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