The aim of the study was to assess the virological/immunological outcome and safety of Saquinavir (SQV), Zidovudine (AZT) and Lamivudine (3TC) therapy in HIV patients. We retrospectively evaluated the charts of 36 HIV patients (male 87% median age 31 yrs, IVDA 72%) who underwent therapy with 5QV (1800 mg/die), AZT (500 mg/die) and 3TC (300 mg/die). 26 (72%) patients were previously on antiviral therapy for at least 16 weeks. No patient ranked in the CDC group. Patients were treated for at least 48 weeks. Hematological indices, changes in CD4+ cell count and plasma HIV-RNA levels were evaluated every 30, 60, and 90 days respectively. At baseline, CD4 cell count and viral load were 230/mcl and 4.55 log respectively for patients previously on therapy and 382/ l and 4.88 log respectively for naive patients. At week 48 the mean CD4+ cell count increase was 70/ l among previously treated and 98/mcl among untreated patients. In respect to the baseline, lower mean HIV-RNA levels were observed at week 12, 24 and 48. No patient showed AIDS-defining events. No patient discontinued therapy due to suspected toxicity. Patients showed a good immunological and virological response, regardless of their previous antiviral treatment. The terapy regimen was safe and well tolerated