The prevalence of HIV-associated neurocognitive disorders (HAND) persists regardless of the use of highly active antiretroviral therapy (HAART), which has proven to be successful in controlling HIV RNA levels. Unlike its effects on viral RNA, its effect on viral DNA levels appears less robust. Based on research in our laboratory, we hypothesize that CD14+/CD16+ monocytes are important viral reservoirs that play a role in HAND neuro-pathogenesis.
The specific aims for this proposed study utilize laser-capture micro dissection of necropsy tissue and cell sorting of peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid cells (CSF);followed by a modified real-time PCR assay to quantitative HIV DNA. We also intend to detect HIV DNA in identifiable cells through the use of unique flow cytometric technologies. We hypothesize that HIV DNA will be the highest within CD14+/16+ monocytes in PBMCs. CSF will also be compared and could provide valuable information about the transition of the virus from the periphery to the CNS. Throughout this study, the expertise of Dr. Bruce Shiramizu along with consultative support from Dr. Amanda Brown (Johns Hopkins University) will be available;both being distinguished HIV researchers.
Our overall goal is to clinically translate these findings to potentially target HIV DNA as a therapeutic option and/or use HIV DNA as a biomarker for HAND. The public health significance of the proposed project impact two areas: 1) Improving the quality of life for individuals afflicted with neurocognitive problems by further our understanding of HAND pathogenesis;and 2) Fulfilling the mission of supporting diversity in health-related research through training of the applicant from an underrepresented group.
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