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We aimed at measuring the adherence to HAART by means of pill count and drug plasma levels. In addition, we aimed at determining variables associated with suboptimal adherence.Prospective observational study of 202 consecutive patients with HIV infection who were receiving antiretroviral treatment, followed up during 9 months. At baseline and at the end of the study a structured questionnaire was administered and a review of medical charts was performed. The adherence was assessed by monthly pill count while drug plasma levels were measured every three months. We considered that a patient adherence was not fulfilled when the mean pill count was90% or when any plasma drug level was lower than that expected.Of 143 available patients, 41.2% were non-adherent. According to the univariate analysis, non-adherent patients were more likely to be younger, female, under a methadone maintenance scheme, under psychiatric treatment, to have depression (according to the Beck Depression Inventory), to have adverse antiretroviral effects and to have a previous history of voluntary withdrawal of the treatment. Men who had sex with other men were significantly more adherent. In the multivariate analysis, female sex [OR 2.6 (1.04-6.65)], to be under a methadone program [OR 9.43 (1.01-88)], to have adverse drug effects [OR 2.63 (1.09-6.33)] and to have a previous history of voluntary withdrawal [OR 2.63 (1.09-6.36)] were independent risk factors for non-adherence.Adherence to antiretroviral therapy was 58.8%, similar to that seen in other chronic diseases. To be under a methadone maintenance program and having an active drug addiction was related with non-adherence. Women with worst adherence levels had frequently psychiatric comorbidity and more adverse drug effects.