Opioid abuse has undergone a resurgence in the last decade. Although many opioids can be swallowed, snorted, or smoked, injectable opioids (especially heroin) have figured most prominently in the HIV epidemic. Injection drug users and their partners and children currently account for 36% of cumulative AIDS cases in the U.S. To improve access to pharmacotherapy for opioid dependence, the federal Drug Addiction Treatment Act (2000) and the Food and Drug Administration (2002) approved buprenrophine for opioid addiction treatment. Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at the kappa opioid receptor. Because mu receptor activation has been shown to stimulate HIV expression in monocytic cells, while kappa receptor activation inhibits HIV expression in these cells, buprenorphine's activity at the kappa receptor may be attenuate HIV expression. This may in turn be important for disrupting the synergistic processes that HIV infection and opioid dependence play in advancing neurocognitive decline. In this proposal, we will test the overarching hypothesis that pharmacological antagonism of kappa opioid receptors, such as that obtained with buprenorphine, may improve neurocognitive function in opioiddependent drug users with HIV infection. We will examine the impact of buprenorphine on changes in neurocognitive (NC) function among opioid-dependent persons with and without HIV-infection, and create a plasma bank to identify biomarkers of neurocognitive changes associated with buprenorphine initiation and maintenance. A cohort of 40 HIV-infected opioid-dependent persons and 40 HIV-seronegative opioiddependent perons newly initiated on buprenorphine will be recruited and serial NC testing will be adminstered and serial blood samples obtained. We will conduct a proteomic analysis to identify biomarkers in platelet poor plasma of buprenorphine administration and neurocognitive outcome in fifteen HIV-infected opioid-dependent persons, using a pre/post design.
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