Funding Opportunity Number: PAR-25-330
Deadline: May 7, 2025
Research Objectives and Scope
This NOFO encourages the characterization of the defective HIV proviral landscape in blood and tissue sites in people living with HIV on ART, the quantification of HIV RNA and protein expression from defective proviruses in vivo, and identification of defective proviral epitopes that drive autologous anti-HIV immune responses. The effects of the defective proviruses on HIV pathogenesis, reservoir dynamics, mechanisms of persistence, post-treatment control, and/or cure strategies will be supported. Methods development will also be supported to optimize viral load measurement, bNAb sensitivity testing, and drug-resistance screening assays to exclude the impact of defective proviruses from those assays. Expertise may be needed in virology, immunology, single-cell multiomics, transcriptomics/proteomics, RNA-Seq, RNA splicing, epitope mapping, HIV reservoir quantification, or technical HIV clinical assay development.
The scope of the research will include basic research, methods development and validation, and the analysis of longitudinal blood and tissue samples from preclinical and clinical studies of people living with HIV and relevant animal models. Clinical trials are not allowed, but human samples are required. The use of samples from clinical trials supported by other funding mechanisms or samples collected from observational studies are encouraged. The use of SIV/SHIV virus models is not considered in scope because of the differences in ratios of defective:intact SIV/SHIV proviruses in primate models vs. in HIV models; applications may only include HIV.
Examples of research activities of interest to NIAID include, but are not limited to:
- Research to quantify defective proviral transcription-/translation-competent reservoirs over time in people living with HIV on ART
- Research to compare defective proviral transcription and/or translation-competent reservoirs between people living with subtype B HIV and people living with other HIV subtypes
- Research to identify and define defective HIV protein epitopes that drive autologous anti-HIV immune responses and characterize the potential relevance of those responses to viral pathogenesis on ART, persistence, reservoir dynamics, post-treatment control, and/or responses to HIV cure strategies
- Research to determine the contributions of defective proviral transcription-/translation-competent reservoirs to the detection of viral blips during ART or viral loads during analytical treatment interruptions
- Research to analyze the effects of defective proviral Env expression on the impact of viral control mediated by therapeutic bNAbs
- Research to determine whether defective provirus integration sites play a role in host cell survival/proliferation or host gene expression
- Research to analyze recombination events when defective provirus-harboring cells are superinfected with replication-competent HIV
- Research to develop clinical assays, such as those used to quantify HIV viral loads, determine viral sensitivities to bNAbs, or to screen for known mutations that confer resistance to ART drugs, that exclude the detection of defective provirus
For more information, please see the opportunity webpage.