OBJECTIVE: The aim of study was to evaluate the influence of pharmacist intervention based on "CMO model", to improve activation in HIV-patients. METHODS: Longitudinal, prospective, single-center study. Eligible patients were HIV-infected, taking antiretroviral treatment. The collected data included demographic characteristics, clinical and HIV-related and pharmacotherapeutic variables. The primary outcome was the variation of patient activation measured by Spanish adapted patient activation measure questionnaire. This questionnaire assesses people's knowledge, skills and confidence in managing their own health care. The assessment was performed at the beginning and 6 months after the program start, which consisted of individualized interventions planned in the stratification model, a motivational interview and a specific pharmacotherapeutic follow-up. RESULTS: A total of 140 patients were included. The most common regimens prescribed were based on non-nucleoside plus nucleoside reverse transcriptase inhibitor (44.0%) and more than half of the patients had chronic concomitant medication. The patients who achieved the highest activation level increased from 28.1% to 68.3% (p<0.0005). The relationship between this increase in patient activation and the stratification level that occurs in largest increases in patients with a low need level, where it was observed an improvement in the percentage of patients with high activation from 28.3% to 74.3% (p<0.001) after intervention. The percentage of patients with adequate adherence to concomitant treatment increased by 18.4% (p = 0.035). Baseline PAM values showed high activation for 28.6% (40 patients), intermediate for 43.6% (61) and low for 27.9% (39). CONCLUSIONS: CMO model has an important role for patient activation, improving adherence and health outcomes for HIV+ patients.