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High levels of adherence do not prevent accumulation of HIV drug resistance mutations

Bangsberg, David Ra,b; Charlebois, Edwin Da; Grant, Robert Mc; Holodniy, Marke; Deeks, Steven Gb; Perry, Sharonf; Conroy, Kathleen Nugentf; Clark, Richardd; Guzman, Davida; Zolopa, Andrewf; Moss, Andrewd

Clinical Science

Objectives: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence.

Methods: Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2.

Results: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92–100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79–100%).

Conclusion: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.

From the aEpidemiology and Prevention Interventions Center, Division of Infectious Diseases and the bPositive Health Program, San Francisco General Hospital, the cGladstone Institute of Virology and Immunology and the dDepartment of Epidemiology and Biostatistics, University of California at San Francisco, the eAIDS Research Center, VA Palo Alto Health Care System and fStanford University School of Medicine, Palo Alto, California, USA.

Requests for reprints to: Dr D. R. Bangsberg, Box 1372, San Francisco General Hospital, UCSF, 1001 Potrero Avenue, Building 100, Room 301, San Francisco, California 94110, USA.

Received: 7 November 2002; revised: 14 March 2003; accepted: 24 March 2003.

© 2003 Lippincott Williams & Wilkins, Inc.