Quantitative assessment of plasma HIV load (RNA copy number) is a powerful predictor of systemic disease progression and response to anti-retroviral therapy. The prognostic value of HIV levels in plasma and CSF for neurologic decline have not been well studied. This may be particularly relevant in an era of potent combination antiretroviral therapy, where the potential exists for complete systemic suppression of HIV, with perhaps brain sequestration and persistent replication. HIV induced neural damage is mediated by products of activated macrophages/microglia. We previously established a cohort of 273 HIV infected subjects, with, or at risk for, neurocognitive abnormalities, utilizing the Dana Consortium, consisting of investigators from 3 institutions: The University of Rochester(UR), Columbia University(CU) and John Hopkins University(JHU). This is the largest, most ethnically, racially and gender diverse cohort assembled to date to study neurologic impairment. We propose: to recruit additional subjects to maintain a cohort of 200 subjects (N=460 over 5 years). Project 1 (CU) will perform cross=sectional and longitudinal analysis to determine if plasma HIV levels and markers of immune activation are independently associated with HIV minor cognitive/motor disorder (HIV- MCMD) or HIV Dementia (HIV-D). Project 2 (JHU) will focus on the prognostic significance of CSF HIV levels for neurologic decline, and examine the relationship between HIV levels and markers of immune activation in plasma, CSF and brain. Project 3 (CU) will determine the relationship between HIV levels, immune activation and severity of functional impairment (neurologic and psychiatric). Core A (UR) will provide administrative functions, data management and biostatistics support. Assays of HIV load (NASBA) and for markers of immune activation for all three projects will be centralized at Core B (JHU). This PPG builds on the existing infrastructure of the Dana Consortium, a consortium with a demonstrated ability to achieve research objectives. The investigators provide complementary expertise for site specific projects. This diverse cohort of subjects with advanced HIV infection provides a unique opportunity to investigate the relationship between virus load, immune activation and the progression of neurologic dysfunction during HIV infection.
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