HAART medication has been implicated as a potential etiopathological source of the increased prevalence of cardiovascular disease (CVD) risk in HIV infected persons. Although recent reports indicate an increasing rate of Hepatitis C virus (HCV) coinfection in the HIV-infected, and HCV infection independently communicates increased cardiovascular risk, the literature has not adequately assessed the possible role of HCV coinfection in cardiovascular pathogenesis in HIV spectrum disease. Comorbid conditions known as dysmetabolic syndrome X are independently associated with both HIV and HCV infection; the syndrome includes alterations in fat deposition, cardiac structure and function, and vascular endothelial function, as well as dyslipidemia and insulin resistance. Two pathophysiological sources in HIV and HCV infected persons is increased pathogen burden and diminished infection surveillance, which result in an elevation of proinflammatory processes. These processes have been shown to induce greater reactive oxygen species formation, which has been linked to atherogenesis and alterations in cardiac and vascular structure and function. Oxidative stress has also been associated with insulin resistance. Because of the possible role of HCV infection and HAART medication in cardiovascular disease risk and because proinflammatory and oxidative factors are likely mediators of this risk, the primary objective of the proposed study is to systematically examine these factors in 420 (of 465 screened) men and women, as a function of HIV and HCV infection, and coinfection. The influence of HAART treatment regimen (anti-retrovirals plus protease inhibitors [PI+] vs. anti-retrovirals without protease inhibitors [PI-]) on these outcomes will be assessed by nesting HAART regimen within the HIV+ groups, thereby yielding a six group comparison (HIV+PI+/HCV+ vs. HIV+PI-/HCV+ vs. HIV+PI+/HCV- vs. HIV+PI-/HCV- vs. HIV-/HCV+ vs. HIV-/HCV-). The secondary objective is to determine whether the data collected is described by the proposed pathophysiological model, which postulates that the burden of exposure to multiple infectious sources is associated with greater levels of proinflammatory factors and oxidative stress, and consequently greater CVD risk and diminished cardiovascular function.