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Randomized Controlled Trial
. 2008 Jan 2;22(1):75-82.
doi: 10.1097/QAD.0b013e3282f366ff.

Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance

Edward M Gardner  1 , Shweta Sharma, Grace Peng, Katherine Huppler Hullsiek, William J Burman, Rodger D Macarthur, Margaret Chesney, Edward E Telzak, Gerald Friedland, Sharon B Mannheimer
Affiliations
Randomized Controlled Trial

Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance

Edward M Gardner et al. AIDS. .

Abstract

Objectives: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance.

Design: A secondary analysis of prospective clinical trial data.

Methods: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance.

Results: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure.

Conclusion: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.

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Conflict of interest statement

Conflicts of interest: None.

Figures

Fig. 1
Fig. 1. Percentage of participants reporting differential adherence at any time during follow-up: overall and by randomized strategy
■ Ever reported; formula imagereported once; □ reported more than once. NNRTI, Non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Fig. 2
Fig. 2. Evaluation of the ‘dose-effect’ of differential adherence: adjusted hazard ratios for participants with differential adherence (once or more than once) compared with participants with no differential adherence in the Community Programs for Clinical Research on AIDS Flexible Initial Retro-virus Suppressive Therapies Study
● Differential adherence once; formula imagedifferential adherence more than once. CI, Confidence interval; Reference group is no differential adherence.
See this image and copyright information in PMC

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