This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposed study has been designed to complement my career development plan and will provide an advanced research practicum experience in which I can apply my newly acquired knowledge of HIV/HCV coinfection, magnetic resonance spectroscopy imaging (MRSI), and neuropsychiatric research methods. It will also serve to provide pilot data for an independent investigator award submission. HIV/HCV coinfection is an emerging, significant comorbidity in neuroAIDS. To date, the neurobehavioral consequences of HIV/HCV coinfection have not been fully characterized although each virus has been shown to independently cause neuropsychiatric disturbance which can be detected by MRSI and neuropsychological testing. The current proposal is designed to investigate whether there is a detectable neuropsychiatric synergy of coinfection and to elucidate the level of HCV viremia that is associated with neurometabolic alterations and cognitive deficits in HIV+ individuals. One hundred HIV/HCV coinfected patients with and without HCV viremia as well as 50 HIV-only and 50 HCV-only patients will receive a MRSI, a psychiatric interview, and a neuropsychologic assessment. The study will test the hypothesis that HCV viremia is associated with increased choline, increased myo-inositol, and increased Glx as well as executive functioning deficits. This study will identify neuropsychiatric and neurophysiologic features of HCV viremia in HIV/HCV coinfection and will serve as a template for neuropsychiatric research of comorbidities in neuroAIDS.
Specific Aims & Hypotheses:
Specific Aim 1 : Determine if a differential effect of HCV viremia in coinfection can be detected in behavior via neuropsychological assessment (specifically, executive dysfunction). Hypothesis 1a: HIV/HCV coinfection is associated with impaired executive function compared to HIV monoinfection and compared to HCV monoinfection. Hypothesis 1b: HIV/HCV viremia is associated with greater executive dysfunction compared to HIV/HCV non-viremic infection.
Specific Aim 2 : Identify whether there is an effect of HCV viremia that can be detected in the frontostriatal brain via neurometabolites. Hypothesis 2a: HIV/HCV is associated with greater frontostriatal neurometabolite alterations (increased Cho, mI, and Glx as well as decreased NAA) in the basal ganglia and frontal neocortex compared to HIV monoinfection and compared to HCV monoinfection. Hypothesis 2b: HCV viremia in coinfection is associated with greater frontostriatal neurometabolite alterations (increased Cho, mI, and Glx as well as decreased NAA) and more severe cognitive impairment compared to HIV/HCV without viremia.
Specific Aim 3 : Investigate the relationship between neurometabolites and cognitive functioning in HIV/HCV coinfection with and without viremia. Hypothesis 3: Neurometabolite alterations (increased Cho, mI, and Glx as well as decreased NAA) will be consistently related to deficits in cognitive functioning and specifically impaired executive function, in HIV/HCV coinfection.
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