Structured treatment interruptions may have beneficial effects on metabolic parameters, while data on anthropometric parameters and on the quality of life are scanty. This study was designed to evaluate the effects of structured treatment interruptions on plasma cholesterol, triglycerides, anthropometric, immunologic, virologic changes and quality of life. A total of 112 HIV-infected patients under HAART with undetectable viremia for longer than 6 months were randomized to undergo 6 cycles of 1-month off and 1-month on therapy or to continue HAART. Patients treated with structured treatment interruptions (STI group) were evaluated monthly, patients in the control group (CTRL group) were evaluated every two months. Anthropometric and quality of life data were collected every four months. The study was designed as a two-arm, prospective, multicentred, controlled trial. Results on the primary endpoints showed a significant decrease in the cholesterol levels in the STI group compared to the CTRL group (total cholesterol median AUC [IQR] was 193.5 mg/dL/month [173.4-209.4], and 210.8 mg/dL/month [194-242.4], respectively, p=0.0009). Although the triglyceride levels were lower in the STI group, the results did not reach statistical significance (triglyceride median AUC [IQR] was 166.8 mg/dL/month [IQR: 112.5-234.9] in the CTRL group, and 169 [IR: 124.7-256.7] in the STI group; p=0.37). As for the secondary endpoints no major differences among groups were noted. Cyclic structured treatment interruptions may have a favorable, although limited, impact on plasma total cholesterol levels in HIV-infected subjects. No modifications of anthropometric and quality of life values were noted.