Occupational therapy holds promise to increase quality of life and social functioning in patients with HIV infection. Since 2000 through 2005, we experimented a complex structured intervention including directly administered HAART, psychiatric support and occupational therapy for 14 patients with advanced HIV infection and multiple disabilities, cared for at an Italian home care facility. Social and occupational abilities were evaluated using the Axis V of DMS-IV, as assessed by the Global Assessment of Functioning Scale. Patients' abilities in coping with stressful situations were examined using the Social Dysfunction Rating Scale. Both outcomes were evaluated in interviews at study entrance and yearly thereafter. As compared to baseline, social function mean score significantly increased by 42% after one year of follow-up, and social stress mean score was significantly reduced by 11%. Both outcomes continued to improve constantly during the entire follow-up. Acceptance of the intervention was high, and three patients got outdoor job positions. The findings from this pilot study suggest that occupational therapy could be integrated with success in the treatment of severely disabled patients with advanced HIV infection. Confirmation from further research is required.