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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
2U24MH100928-06
Application #
9534230
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Colosi, Deborah
Project Start
2013-05-01
Project End
2023-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Dubé, Karine; Gianella, Sara; Concha-Garcia, Susan et al. (2018) Ethical considerations for HIV cure-related research at the end of life. BMC Med Ethics 19:83
Guha, Debjani; Mukerji, Shibani S; Chettimada, Sukrutha et al. (2018) CSF extracellular vesicles and neurofilament light protein as biomarkers of CNS injury in HIV-infected patients on antiretroviral therapy. AIDS :
Anderson, Ariana E; Jones, Jacob D; Thaler, Nicholas S et al. (2018) Intraindividual variability in neuropsychological performance predicts cognitive decline and death in HIV. Neuropsychology 32:966-972
Marquine, María J; Flores, Ilse; Kamat, Rujvi et al. (2018) A composite of multisystem injury and neurocognitive impairment in HIV infection: association with everyday functioning. J Neurovirol 24:549-556
Mukerji, Shibani S; Misra, Vikas; Lorenz, David R et al. (2018) Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Clin Infect Dis 67:1182-1190
Premeaux, Thomas A; D'Antoni, Michelle L; Abdel-Mohsen, Mohamed et al. (2018) Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals. J Neurovirol :
Sundermann, Erin E; Heaton, Robert K; Pasipanodya, Elizabeth et al. (2018) Sex differences in HIV-associated cognitive impairment: an observational cohort study. AIDS :
Chettimada, Sukrutha; Lorenz, David R; Misra, Vikas et al. (2018) Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy. Sci Rep 8:7227
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
Letendre, Scott; Bharti, Ajay; Perez-Valero, Ignacio et al. (2018) Higher Anti-Cytomegalovirus Immunoglobulin G Concentrations Are Associated With Worse Neurocognitive Performance During Suppressive Antiretroviral Therapy. Clin Infect Dis 67:770-777

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