HIV transmission risk behaviors are common and recalcitrant among persons with methamphetamine (METH) dependence, but their underlying cognitive and neurobiological mechanisms are not well understood. During the previous funding period we learned that METH dependence may differentially impact the expression of inhibitory deficits related to risk taking in the setting of HIV infection in humans and mouse models. Building on this work, the current application requests support for parallel human and animal research to determine the individual and combined effects of METH dependence, HIV infection and aging on risk taking. We will leverage our expertise in implementing cross-species measures by evaluating several important components of risk taking that will be isolated paradigmatically in humans and two mouse models of HIV: 1) Preference for risk, reward and/or novelty versus punishment avoidance, 2) motivation defined as willingness to work for a reward, and 3) inhibition. In the human study, we will test our hypothesis HIV and METH have differentiable effects on the multiple components that underlie risk taking in all 320 well-characterized subjects from the TMARC cohort that will be stratified by METH dependence, HIV serostatus, and age. We will also examine the impact of aging on the expression of risk behaviors in HIV and METH, as well as the unique effects of risk taking and its components on real-world outcomes (e.g., adherence) in our clinical groups. Shared human subjects with TMARC Project 2 will allow us to examine the neural substrates of risky decision-making, including neuroimaging indices of functional connectivity and white matter injury. The animal studies will employ two mouse models of HIV (i.e., constitutive gp120tg and conditional iTat-tg) with and without METH treatment that will be evaluated with cognitive paradigms that map directly on to those used with our human subjects. Collaborations with the TMARC Neuroimaging and Neuroscience and Animal Models Cores will us to parse out biological mechanisms of these critical cognitive functions in mouse models. The ultimate goal of this research is to propel the design prevention efforts that target specific components of risk taking in order to reduce HIV transmission.
Risk taking behavior is common in persons with HIV and methamphetamine dependence. The ultimate goal of this cross-species study of humans and mice is to facilitate the design of treatment and prevention efforts that target the specific cognitive components of risk taking in HIV and methamphetamine in order to reduce HIV transmission.
|Soontornniyomkij, Virawudh; Umlauf, Anya; Soontornniyomkij, Benchawanna et al. (2018) Association of antiretroviral therapy with brain aging changes among HIV-infected adults. AIDS 32:2005-2015|
|Thaney, Victoria E; Sanchez, Ana B; Fields, Jerel A et al. (2018) Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research. J Neurovirol 24:156-167|
|Kesby, James P; Chang, Ariel; Markou, Athina et al. (2018) Modeling human methamphetamine use patterns in mice: chronic and binge methamphetamine exposure, reward function and neurochemistry. Addict Biol 23:206-218|
|Hoenigl, Martin; Jain, Sonia; Moore, David et al. (2018) Substance Use and Adherence to HIV Preexposure Prophylaxis for Men Who Have Sex with Men1. Emerg Infect Dis 24:|
|Moore, David J; Pasipanodya, Elizabeth C; Umlauf, Anya et al. (2018) Individualized texting for adherence building (iTAB) for methamphetamine users living with HIV: A pilot randomized clinical trial. Drug Alcohol Depend 189:154-160|
|MacDuffie, Katherine E; Brown, Gregory G; McKenna, Benjamin S et al. (2018) Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume. Neuroimage Clin 20:1044-1052|
|Stecher, M; Chaillon, A; Eis-Hübinger, A M et al. (2018) Pretreatment human immunodeficiency virus type 1 (HIV-1) drug resistance in transmission clusters of the Cologne-Bonn region, Germany. Clin Microbiol Infect :|
|Stecher, Melanie; Chaillon, Antoine; Eberle, Josef et al. (2018) Molecular Epidemiology of the HIV Epidemic in Three German Metropolitan Regions - Cologne/Bonn, Munich and Hannover, 1999-2016. Sci Rep 8:6799|
|Oppenheim, Hannah; Paolillo, Emily W; Moore, Raeanne C et al. (2018) Neurocognitive functioning predicts frailty index in HIV. Neurology 91:e162-e170|
|Walker, Keenan A; Brown, Gregory G (2018) HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis. J Clin Exp Neuropsychol 40:357-376|
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