HIV Drug Resistance: Genotype-Phenotype-Outcome Correlations (R01 Clinical Trial Not Allowed) | RFA AI 18 029

Opportunity Information: Apply for RFA AI 18 029

This NIH funding opportunity (RFA AI 18 029) supports research focused on understanding how HIV drug resistance affects whether treatment works in real-world clinical care. It is an R01 grant mechanism under the health funding category (CFDA 93.855) and is explicitly labeled "Clinical Trial Not Allowed," meaning applicants should propose studies that do not involve prospective assignment of human participants to interventions. Instead, the announcement is aimed at research that can clarify how laboratory measures of resistance line up with patient outcomes, helping improve the way resistance testing is interpreted and used when selecting or adjusting antiretroviral therapy.

The scientific emphasis is on connecting three pieces of evidence into a clearer chain: viral genotype (the resistance mutations present in HIV's genetic sequence), viral phenotype (how those mutations actually change the virus's susceptibility to drugs in lab-based assays), and clinical outcomes (treatment success or failure on recommended regimens). The announcement particularly encourages proposals that examine genotype-phenotype correlations across diverse HIV subtypes, reflecting the reality that global HIV diversity can affect how resistance mutations behave and how well interpretation algorithms perform. A major theme is improving understanding of resistance beyond the most common subtype contexts, so that resistance interpretation is more accurate for different populations and geographic regions.

Another core priority is the role of minority variant resistance, meaning resistance mutations that exist at low frequencies within a person's viral population and may be missed by standard testing approaches. The FOA seeks studies that investigate whether these low-abundance mutations meaningfully predict treatment outcomes, under what circumstances they lead to failure, and which drug classes or regimens are most sensitive to their presence. This focus reflects ongoing clinical uncertainty about when minority variants should change treatment decisions, and it invites careful work that ties sensitive laboratory detection (for example, deep sequencing approaches) to well-characterized clinical endpoints.

The announcement also highlights the problem of discordance between genotype and treatment success or failure. In practice, a patient's genotype may suggest resistance, yet the patient still suppresses virus, or the genotype may look favorable but the regimen fails. Applications are encouraged to dig into the reasons behind these mismatches. That could include biological explanations (such as compensatory mutations, fitness costs, subtype-specific mutation effects, or complex mutation patterns), pharmacologic factors (drug levels, adherence patterns, drug-drug interactions), clinical factors (baseline viral load, prior treatment history), and limitations of current interpretation methods. The goal is to explain why genotype does not always translate cleanly into outcome, and to generate evidence that can improve predictive models and decision support tools.

A practical and strongly encouraged approach is laboratory evaluation of viral samples that have strong clinical correlates, particularly from patients taking recommended antiretroviral regimens. In other words, the program is looking for studies that pair robust lab testing (genotyping, phenotyping, or both) with high-quality clinical data, so that findings are not purely theoretical. This can include analyses of stored samples linked to treatment histories and outcomes, cohort-based studies, or other observational designs where the clinical trajectory is well documented, as long as the work does not cross into an interventional clinical trial.

From an administrative standpoint, this is a discretionary NIH grant with an award ceiling listed at $500,000, with the original closing date noted as 2018-12-05 and a creation date of 2018-07-24. The opportunity is open to a broad range of applicants, including various levels of government (state, county, city/township, special districts), public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and other entities. It also explicitly calls out additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIS institutions, Hispanic-serving institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, tribal governments and tribal organizations (including those other than federally recognized), faith-based or community-based organizations, U.S. territories or possessions, eligible federal agencies, and non-U.S. entities and regional organizations. This broad eligibility aligns with the global and cross-population relevance of HIV resistance research and encourages participation from institutions serving diverse communities.

Overall, the opportunity is designed to strengthen the evidence base that links resistance mutations to drug susceptibility and to real treatment outcomes, especially in settings where current tools are less predictive. By supporting studies on subtype diversity, minority variant mutations, and genotype-outcome discordance, the FOA aims to improve how clinicians and public health programs interpret resistance data and choose therapies that are most likely to succeed.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "HIV Drug Resistance: Genotype-Phenotype-Outcome Correlations (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2018-07-24.
• Applicants must submit their applications by 2018-12-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA AI 18 029

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