ObjectivesOur objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20-month period and its relationship with virologic success.MethodsSelf-reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitor–containing regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined.ResultsAmong the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was “always,” 225 (51.6%) “sometimes,” and 74 (17.0%) “never” “highly adherent” during follow-up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64–5.58]) or sometimes (OR [95% CI], 2.15 [1.24–3.74]) “highly adherent.”ConclusionAdherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.