BACKGROUND: With the advent of antiretroviral therapy regimens in HIV positive patients, it is crucial to consider their long-term benefits to risk ratios. The responsibility of treatment in premature atherosclerosis is not clear. Thus, the aim of this study is to evaluate the impact of exposure to reverse transcriptase inhibitors (nucleosidic and non-nucleosidic) and to protease inhibitors on the cardiovascular status of an entire hospital based cohort of patients. METHODS: 154 patients were included. Using a linear analysis, we sought an association between the cumulative time of exposure to these three classes of antiretroviral drugs and the carotid intima-media thickness measured by ultrasonography and a cardiovascular composite score. RESULTS: The study confirms premature atherosclerosis, which not only correlates with the usual risk factors, such as triglyceride level, but also with protease inhibitor exposure, especially that of lopinavir. Nevertheless as regards current drug exposure, the clinical impact was low: five clinical complications of atherosclerosis and only one out of 35 scintigraphic and ECG exercise tests warranted a coronary angiography which was negative. CONCLUSION: These data should not lead to the rejection of protease inhibitors but should strengthen the prevention of cardiovascular diseases as an integral part of the management of HIV patients.