DESCRIPTION (provided by applicant): Data from the Strategies for Management of Antiretroviral Therapy (SMART) study indicate that episodic use of antiretroviral treatment (ART) is associated with an increased risk of cardiovascular disease (CVD). The general aim of this ancillary study proposal is to elucidate mechanisms underlying the increased CVD risk in the episodic ART treatment arm of SMART. Three subsamples of the 5,472 trial participants have been identified for measurement of lipid particle number and size by nuclear magnetic resonance (NMR) spectroscopy and for measurement of selected inflammatory and coagulation markers: 1) a random sample of 500 participants randomized to the episodic and viral suppression treatment arms; 2) 250 participants who were ART-na¿ve entry or who had not taken ART for at least 6 months prior to randomization in SMART; and 3) participants who developed CVD (208 cases) and two matched controls (416 participants) for each case. We will take advantage of the trial infrastructure, participant data that will be collected through mid-2007, and the large specimen repository for SMART to efficiently address three aims based on these subsamples. With the extensive and high quality SMART dataset, and the track record of our multidisciplinary team, the findings from this research can be expected to elucidate reasons for increased CVD risk among HIV-infected individuals and advance our understanding of the pathophysiology of CVD in the presence of HIV. Advances in the management of HIV disease and in ART over the last 10 years have let to prolonged disease-free survival in a substantial proportion of individuals with HIV infection. This proposal will produce additional information that will enhance their disease-free survival rate. (End of Abstract)