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Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial

Gardner, Edward Ma; Hullsiek, Katherine Hb; Telzak, Edward Ec; Sharma, Shwetab; Peng, Graceb; Burman, William Ja; MacArthur, Rodger Dd; Chesney, Margarete; Friedland, Geraldf; Mannheimer, Sharon Bg; for the Terry Beirn Community Programs for Clinical Research on AIDS and the International Network for Strategic Initiatives in Global HIV Trials

doi: 10.1097/QAD.0b013e328335cd8a
Clinical Science

Objective: To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance.

Design: Secondary analysis of prospective clinical trial data.

Methods: Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis.

Results: Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95% confidence interval (CI) 0.9–1.4 per 10% lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95% CI 1.1–1.3 per 10% lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure.

Conclusion: Adherence–resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.

aDenver Public Health, Denver, Colorado, USA

bUniversity of Minnesota, Minneapolis, Minnesota, USA

cBronx Lebanon Hospital Center, Bronx, New York, USA

dWayne State University, Detroit, Michigan, USA

eUniversity of Maryland Medical Center, Baltimore, Maryland, USA

fYale University School of Medicine, New Haven, Connecticut, USA

gHarlem Hospital, Columbia University College of Physicians & Surgeons, New York, New York, USA.

Received 5 October, 2009

Revised 18 November, 2009

Accepted 20 November, 2009

Correspondence to Edward M. Gardner, MD, Denver Public Health, 605 Bannock Street, Denver, CO 80204, USA. Tel: +1 303 602 8740; fax: +1 303 602 8739; e-mail: edward.m.gardner@dhha.org

© 2010 Lippincott Williams & Wilkins, Inc.