This is a renewal application for the California NeuroAIDS Tissue Network (CNTN) in response to RFA-MH-18- 250. CNTN is an active participant in the National NeuroAIDS Tissue Consortium (NNTC), a partnership of four NIH-funded neuroAIDS tissue banks. The overarching objectives of the CNTN remains the same today as it was when it was first established in 1998 and encompass the 1) recruitment, clinical assessment, and follow- up of a late-stage HIV cohort, and 2) collection, maintenance, and distribution of specimens to investigators interested in conducting research on the neuropathogenesis of HIV-induced central and peripheral nervous system dysfunction. For the current application, and to address these objectives, CNTN will continue to maintain an in-life cohort of at least 150 participants (mostly people living with HIV/AIDS, PLWHA) with the purpose of obtaining autopsies from high priority cases that are aligned with the three thematic priorities in the RFA: a) HIV eradication from CNS reservoirs; b) mechanisms of HIV-associated neurocognitive disorders (HAND) in the setting of long-term HAART, and c) understanding comorbidities associated with HIV, including the effects of aging and chronic HIV-infection. CNTN will accumulate and manage a bank of in-life (plasma, CSF, blood, stool) and autopsy (brain, heart, lung, liver, kidney, lymph node, blood, and CSF) specimens and data from a cohort of persons living with HIV who are well characterized neuropsychologically, neuromedically, and psychiatrically. CNTN will additionally collect tissues (e.g., gut lymphoid tissue, testes) for emerging CNS cure and eradication research, and stool for microbiome research. Unique within the NNTC, the CNTN has assumed responsibility for CNS HIV-1 Antiretroviral Therapy Effects Research (CHARTER) specimens including plasma, CSF, buccal swabs, skin biopsies, and nucleic acids. De-identified CHARTER data sets (clinical, laboratory, genetic, neuroimaging, and research) have been transferred to the NNTC Data Coordinating Center (DCC), where they are now maintained. CNTN will maintain both the CNTN and CHARTER specimen resource abiding by strict quality assurance and quality control procedures, and will provide timely transfer of data and specimen inventories to the NNTC Data Coordinating Center (DCC). External requests for de-identified CNTN or CHARTER data or specimens are now managed by the DCC in collaboration with NNTC sites, and the CNTN team is well equipped to provide timely distribution of both CNTN and CHARTER specimens according to NNTC data and resource distribution policies. Finally, CNTN will continue to be an active collaborating member of the NNTC by: coordinating with the DCC and other NNTC sites; providing scientific and technical expertise to the wider research community as a voting member of the NNTC Steering Committee (SC), which reviews requests for data and specimens to facilitate neuroAIDS research; and as the leader of the NNTC Neuropsychology/Psychiatry subcommittee. Through the accomplishment of these objectives, the CNTN will continue to be a national and international resource serving the needs of neuroAIDS investigators.
HIV-associated neurocognitive disorders (HAND) remain prevalent in the era of effective antiviral therapy for HIV. The CNTN, as part of the NNTC, provides neuromedical, neurocognitive, and psychiatric characterization in-life and gathers brain and other tissues upon death. CNTN and CHARTER data, fluids and tissues are made available to qualified investigators worldwide and are essential to uncovering the mechanisms associated with persistence of HAND, which will benefit our understanding of those living with HIV.
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