OBJECTIVES: We measured adherence to and satisfaction with anti-HIV treatment and quality of life (QoL) of a sample of Italian patients (pts). METHODS: We carried out a perspective, multicentre observational survey. Pts who needed a simpler antiretroviral treatment were asked to fill in both a questionnaire for measuring adherence/satisfaction with therapy (PMAQ-7) and a QoL one (MOS-HIV). Questionnaires were administered at baseline (change of therapy) and 3 months later. RESULTS: From March to December 2001, 45 centres enrolled 407 pts (285 fully evaluable). Males were 69.5%, mean age was 38 years. HIV infection was mainly due to IV drug use (44%) and heterosexual intercourse (36%). Baseline treatments were: 2NRTI + 1 or more PI (68%), 2NRTI + 1NNRTI (12%), 3NRTI (10%), other (10%). Treatments changed as follow: 2NRTI + 1 or more PI (20%), 2NRTI + 1NNRTI (33%), 3NRTI (43%; in this group 102 out of 122 pts, 84%, on Trizivir), other (5%). Reasons for changing therapy (multiple reasons allowed) were high pill burden (45%), side effects (29%), high number of assumptions (26%), failure due to poor compliance (18%), dietary requirements (17%), fixed time of assumption (12%), other (13%). After switching, scores of both questionnaires increased in all pts, meaning better compliance and QoL. Effect sizes (ES) of PMAQ-7 score showed that the highest values were related to PMAQ-7 adherence (0.28) and scheduling (0.75); highest values were reported in scheduling among pts treated with 3NRTI (ES 1.01). Highest ES of MOS-HIV were in health transition (0.5) and MOS-HIV QoL (0.38); highest values were reported in health transition among pts treated with 3NRTI (ES 0.69). CONCLUSIONS: We conclude that a simpler therapy could improve both HIV patient adherence and QoL.