The National Institute on Drug Abuse (NIDA) is inviting research proposals under the “Advancing Research on Molecular Targets and Mechanisms that Influence the Interplay Between Sex Hormones, HIV, and Addictive Substances” funding opportunity, which uses the R21 grant mechanism. This opportunity focuses on exploratory studies to understand how sex hormones impact HIV progression in individuals with substance use disorders (SUDs), specifically examining the biochemical pathways influenced by sex hormones that may contribute to HIV and addiction outcomes. The R21 mechanism is suitable for high-risk, high-reward projects, particularly those without preliminary data, as this funding aims to stimulate innovative research on the interplay between sex hormones, HIV, and addictive substances.

Research under this NOFO should investigate molecular and biochemical mechanisms by which sex hormones, such as estrogen, progesterone, and testosterone, affect HIV dynamics, including replication, latency, and response to antiretroviral therapy (ART) in the presence of addictive substances. Specific areas of interest include how sex hormones influence the establishment of HIV reservoirs, neural and synaptic impairments caused by HIV and drug use, and how these hormones impact relapse behaviors and drug-seeking tendencies in the context of HIV and SUD comorbidity. The research scope excludes social, behavioral, or environmental factors, instead requiring a focus on the molecular and biochemical interactions between sex hormones, HIV, and substances like opioids, stimulants, cannabinoids, and others (excluding alcohol).

Applicants are required to submit a Plan for Enhancing Diverse Perspectives (PEDP), detailing strategies to incorporate diverse scientific viewpoints, research backgrounds, and geographic diversity in the research team and project. The PEDP is integral to the scientific merit evaluation process, and applications without a PEDP will be administratively withdrawn prior to review. The PEDP should include plans for collaborative frameworks with varied institutions, inclusive recruitment of research participants, and development opportunities for early-career researchers, especially those from underrepresented backgrounds.

NIDA plans to allocate $3 million in FY 2026 for this R21 and its companion R01 NOFO (RFA-DA-26-007), funding an estimated 4–6 projects. For R21 applications, direct costs are capped at $275,000 over a maximum project period of two years, with no more than $200,000 allowable in any single year. Applications should clearly justify their budget in line with the research objectives and the scope of the proposed project.

Eligible applicants include U.S.-based and foreign institutions, including public or private higher education institutions, nonprofits, for-profit entities, and local or state government bodies. Non-domestic components of U.S. organizations are also eligible to apply. All applicants must complete necessary registrations in the System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code, and eRA Commons prior to submission.

Applications are due by March 13, 2025, with a recommended letter of intent due by February 12, 2025, to assist NIDA in planning the review process. The application must include specific details about the relevance and potential impact of the proposed research on understanding HIV-SUD comorbidity through the lens of sex hormones. The scientific merit review will evaluate the significance, innovation, rigor, feasibility, investigator expertise, and research environment, as well as how well the PEDP aligns with the project’s aims.