Presenter
Vasudev Rao, M.B.B.S., M.S.
Division of AIDS Research
Goal
The National NeuroHIV Tissue Consortium (NNTC) was established in 1998 to support research to further understand HIV-associated central nervous system dysfunction. This Consortium is currently co-funded by NIMH, NINDS, NIDA, and NIA, and provides prospective clinical data and well-characterized biological specimens, including post-mortem tissue, to investigators studying HIV-induced neuropathogenesis in the context of anti-retroviral therapy (ART), the comorbidities of aging, including cardiovascular and metabolic disease, and HIV cure efforts. Specifically, the NNTC serves to collect, store, and provide as a resource longitudinal clinical data, well-characterized biospecimens, and post-mortem central nervous system and peripheral tissue donated by people with HIV and HIV-negative volunteers. Through a contract mechanism, this concept aims to sustain and modernize the NNTC, a national resource no single institution could replicate.
Rationale
HIV-associated Central Nervous System (CNS) dysfunction continues in the ART era, impacted directly by HIV in the brain as well as by long-term treatment effects and the comorbidities of aging, vascular disease, neurodegeneration, substance use, frailty, and traumatic brain injury. The NNTC resource mirrors the changing face of the HIV epidemic and helps to expand the knowledge base for NeuroHIV research globally. The Consortium is organized as five clinical sites, coordinated by a central Coordination and Analytics Hub (CCAH). The clinical sites are responsible for recruitment, clinical assessment, and follow-up of the cohort, and for the collection, characterization, maintenance, and distribution of biospecimens and post-mortem tissue. The CCAH provides expertise in data coordination, harmonization, and analytics, maintains the resource catalog and request workflows, and supports an independent Scientific Core, while final contractual decisions remain with the Government. Comprehensive neuromedical, neuropsychological, psychiatric, and virological data are collected antemortem from a cohort recruited for analytic balance across the mechanisms driving heterogeneous brain-health outcomes; post-mortem samples are clinically annotated and characterized by standardized neuropathology. The NNTC also incorporates data from the multi-site CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study.
To date, the NNTC has enrolled more than 3,900 participants, banked post-mortem tissue from more than 1,600 donors, and enabled more than 1,000 publications and 1,050 investigator requests worldwide, among the most deeply characterized neuroHIV resources available. Its distinctive value lies in linking decades of longitudinal clinical characterization to post-mortem CNS tissue for the same individuals, enabling questions that neither clinical cohorts nor tissue banks can address alone. For example, among donors with well-controlled virus in the blood, HIV can still be detected within brain tissue, underscoring the central nervous system as an important site for research on HIV persistence and cure.
This renewal aims to continue and modernize the NNTC as a critical resource for catalyzing high-priority research in NeuroHIV, including studies of HIV neuropathogenesis, aging with long-term HIV and ART, and research toward an HIV cure. This project has been successful because of clear government priorities, well-defined quality standards, and program continuity, and continuation of this valuable resource would ensure sustained scientific benefit to NIH. The renewal is proposed as an open competition so that the most capable performers may be selected, while the established structure, five or more clinical sites coordinated by a central Coordination and Analytics Hub, is expected to continue, as it meets the Government’s need for standardized, cross-site, quality-controlled collection and distribution. Deeper phenotyping of the aging population with HIV requires additional longitudinal and biospecimen data beyond what the current cohort provides, which is the principal need driving the re-competition. The Government anticipates continued enrollment and characterization of a balanced cohort weighted toward people with HIV, with an approximate target of 65% of people with HIV and 35% appropriately matched controls that may be adjusted to reflect the needs of requesting investigators. The cohort will remain inclusive of men and women and of populations disproportionately affected by HIV, with a focus on the aging population with HIV, and biospecimens and linked data will be collected and distributed to qualified investigators nationwide. Specific quantities will be defined in the solicitation.
In the renewal period, the re-competed program will advance current NIH priorities by delivering an AI-ready, reproducibility-oriented NeuroHIV data ecosystem; integrating electronic health record data for clinical continuity between visits; resolving the cohort into treatable-trait phenotypes for trial readiness; and sustaining rapid autopsy to yield viable, reservoir-relevant human CNS tissue, moving the NNTC from a well-characterized repository toward a mechanism-ready platform. Because a national resource of this kind requires guaranteed deliverables, Government-directed priorities, enforceable continuity, and defined quality standards, it is proposed for continuation through a solicitation of requests for proposals (RFP) administered through a contract mechanism.
