Microglial Pathophysiology in Comorbid Substance Use Disorder (SUD) and HIV (R61/R33 Clinical Trial Not Allowed)

The National Institute on Drug Abuse (NIDA) seeks applications for research focused on microglial pathophysiology in individuals with comorbid HIV and Substance Use Disorder (SUD). This grant aims to fund studies examining the interactions of HIV-infected microglia with protein networks that contribute to cell type- and region-specific disruptions in brain signaling. Research should investigate how HIV and SUD jointly alter microglial protein expression and cell signaling, which has been linked to distinctive cognitive and neuro-pathologies in affected individuals. The funding opportunity follows an exploratory R61/R33 phased approach, with the initial R61 phase focusing on establishing methods for profiling protein interactions, and the R33 phase expanding these methods in in vivo models to study protein signaling dynamics within microglial networks. Projects will ideally utilize cutting-edge proteomics to identify and quantify host-virus and host-host protein interactions in microglia. Research is expected to generate specific protein interaction profiles from brain regions implicated in SUD and HIV, with a focus on microglial influence on neural circuits affected by the conditions. Successful projects will deliver mechanistic insights into region-specific disruptions and microglial roles in signaling pathways, potentially leading to targeted interventions for comorbid HIV/SUD. NIDA encourages the use of organismal models (including human CNS samples or nonhuman primates) that replicate complex pathophysiological features seen in this comorbidity, aiming for results that may inform new therapies or a future HIV cure. The grant provides up to $2.5 million in FY 2026 to support 3-6 projects, with a maximum project period of five years. Application budgets should reflect the project’s actual needs and will be subject to NIH policies on allowable costs. Higher education institutions, nonprofits, government entities, tribal organizations, and international entities are eligible. Applicants must have completed registrations with SAM, NCAGE (for foreign entities), eRA Commons, and Grants.gov before submission. A letter of intent is encouraged by July 14, 2025, and full applications are due by August 14, 2025. Applications must adhere to NIH guidelines, utilizing updated FORMS-I, and should emphasize quantitative milestones for assessing progress. Proposed studies must involve repeated drug exposure models, cannot rely solely on in vitro models, and must avoid focusing exclusively on alcohol use. NIDA recommends alignment with its special funding considerations, as noted in the NOFO, for more successful application outcomes. Reviewers will evaluate based on significance, innovation, rigor, feasibility, and investigator qualifications, with special attention to the importance and scientific value of addressing this research gap. The submission process requires thorough compliance with NIH’s application guidelines, including data sharing plans and addressing biological variables. Applications will undergo NIH’s dual review process, with peer review and advisory council stages assessing scientific merit, feasibility, and alignment with NIH priorities. Applicants are encouraged to monitor submissions for errors and use NIH resources for support.