SCIENTIFIC REVIEW AND EVALUATION AWARD

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The HIV epidemic is a major public health problem in the United States and the world. Nervous disease is a frequent cause of morbidity and mortality for the more than 1 million people infected with HIV in the U.S. Recently, with the success of protease inhibitor therapy in the treatment of systemic HIV disease and the limited penetration of protease inhibitors into the nervous system, there is a developing awareness that CNS disease may become of even more importance in the clinical management of HIV disease and the HIV epidemic. Although heavy alcohol use, which has its own CNS and PNS toxicity, is common in populations at high risk for HIV infection, almost no research directly addresses the effect of heavy alcohol use on HIV disease severity and progression. The primary goal of this Program Project is to determine the effect of chronic heavy alcohol use on CNS and PNS morbidity in HIV disease. This effect may result from behavioral and biological effects of chronic alcohol use increasing the rapidity of the progression of the overall HIV disease process or decreasing the response to HIV treatment and from alcohol's own nervous system toxicity. These mechanisms and their effects will be evaluated in a longitudinal study of HIV+ and HIV-chronic heavy drinkers (HIV+ HDs & HIV-HDs) and light/non-drinkers (HIV + L/NDs & HIV-L/NDs). The Program Project goals are to: . Determine whether HIV+ HDs have decrease care seeking and HIV treatment adherence, an increased prevalence of unprotected sex, poorer nutrition, and/or decreased drug levels of HIV treatment medications. . Determine whether a) HIV + HDs have a greater rate of HIV systemic disease progression or reduced treatment response, and b) the degree to which the behavioral and drug metabolism effects of chronic heavy drinking underlie any increased rate of HIV systemic disease progression or reduced treatment response. . Determine whether HIV+ HDs have greater CNS and PNS morbidity and progression of such morbidity than HIV+ LDs. Determine whether these effects of chronic heavy alcohol use are additive or exceed additive effects. . Determine the impact of CNS and PNS morbidity on the quality of life of HIV+ individuals. . In HIV+ subjects, determine the association of CNS and PNS morbidity and its progression with systemic measures of viral load, immune suppression and nutritional status, and with CSF measures of CNS disease, and determine whether these associations differ between heavy chronic alcohol drinkers and light/non-drinkers. We will study four groups of subjects: 120 HIV+ HDs, 120 HIV+ L/NDs, 60 HIV-HDs, and 60 HIV-L/NDs.