Concepts represent early planning stages for program announcements, requests for applications, or solicitations for Council's input. If NIAID publishes an initiative from one of these concepts, we link to it below. To find initiatives, go to Opportunities & Announcements.
NB: Council approval does not guarantee that a concept will become an initiative.
Table of Contents
- Targeted In Vivo Delivery of Gene Therapeutics for HIV Cure
- Next Generation Biologics for Sustained HIV Remission
- NIH AIDS Reagent Program
- HIV Drug Resistance: Genotype-Phenotype-Outcome Correlations
- NIAID Virology Quality Assurance (VQA) Program
- Halting TB Transmission in HIV-Endemic Settings
- Understanding Immunopathogenesis of Tuberculosis in HIV-1 Infected and Exposed Children
- Harnessing Big Data To Halt HIV
- Imaging the Persistent HIV Reservoir
- Optimizing Phylodynamics To Target and Interrogate Clusters (OPTICS)
For the published request for applications, see the April 20, 2018 Guide announcement, Targeted In Vivo Delivery of Gene Therapeutics for HIV Cure (R01 Clinical Trial Not Allowed).
For the published request for applications, see the April 11, 2018 Guide announcement, Next-Generation Biologics for Sustained HIV Remission (R01 Clinical Trial Not Allowed).
Request for Proposals—proposed FY 2019 initiative
Contact: Kishan Patel
Objective: The objective of the NIH AIDS Reagent Program (ARP) is to facilitate HIV/AIDS research by providing access to standardized state-of-the-art reagents, technology, and other research resources to investigators around the world.
Description: This initiative will provide continued support for a contract to acquire state-of-the-art HIV/AIDS-related research and reference reagents; produce reagents, standardized panels, and protocols; and provide these reagents at minimal cost to qualified investigators throughout the world. Additionally, the ARP collects information about AIDS-related reagents and standards and disseminates this information to the research community, enhances technology transfer and publication of methods, and facilitates the availability of reagents through proactive communication with biotechnology and pharmaceutical companies.
Request for Applications—proposed FY 2019 initiative
Contact: Keith Crawford
Objective: The objectives of this initiative are to provide data to better evaluate correlations between HIV drug resistance genotype, in vitro phenotype of the virus (i.e., drug susceptibility), and virologic outcome (i.e., virologic success or failure). Applications are sought in three specific areas:
- To better elucidate the role of minority variants in the development of resistance to antiretroviral drugs, and the effect of minor variants on virologic outcomes in both B and non-B subtypes. Standard genotypic resistance tests use Sanger sequencing to identify drug resistance mutations but can only detect mutations present at greater that 15 percent frequency of an individual’s quasispecies. Some studies suggest that mutations present at 1 percent or less may result in clinical treatment failure.
- To understand genotype/phenotype/outcome correlations in non-B subtypes. Non-B subtypes may have naturally-occurring polymorphisms that confer resistance to certain antiretrovirals. Resistance mutations may also have different effects (differences in fold-sensitivity to a drug) across subtypes. Some subtypes appear to display intrinsically reduced susceptibility to certain antiretroviral drugs, increasing the risk of failure.
- To better understand why some nucleoside reverse transcriptase inhibitors maintain activity and help prevent virologic failure in protease inhibitor-based regimens, in the presence of drug resistance mutations.
Description: Projects that will be supported include:
- Studies focused on determining the biological basis for treatment success in settings where resistance is predicted by genotypic drug resistance results.
- Studies focused on determining the biological basis for treatment failure in the setting where resistance is not predicted by standard genotypic testing and adherence is thought to be optimal.
- Studies of genotype/phenotype/clinical outcome correlations across various clades/subtypes (including in vitro studies utilizing clinical samples) and different agents and combinations of agents.
- Studies of the contribution of minor variants to drug susceptibility and virologic outcome and the point at which minor variants become clinically relevant.
For the above types of studies, investigators are encouraged to test in vitro susceptibility of viruses with combinations of mutations found in clinical specimens and to test not only in the presence of single drugs, but also with relevant combinations of antiretroviral drugs.
This initiative will not support:
- Clinical trials, although the use of samples from prior clinical trials is encouraged.
- Development of new cohorts but use of samples from established cohorts is permitted.
- Surveys of resistance, although samples from surveys could be used in some studies.
- Studies primarily focused on adherence.
- Studies of HIV resistance to neutralizing antibodies or other biologicals.
- Cost analysis studies.
For the published requests for proposals, see the May 2, 2018 solicitation, NIAID Virology Quality Assurance (VQA) Program.
Request for Applications—proposed FY 2019 initiative
Contact: Sudha Srinivasan
Objective: The objectives of this request for applications are to promote research toward:
- Understanding of the critical drivers of tuberculosis (TB) transmission at the individual level and expanded to members of the Transmitter-Recipient Cluster Chains (TRCC) in HIV-infected populations.
- Potential interventions to prevent TB transmission underpinned by an increased understanding of the underlying biologic mechanisms.
- Understanding of biomedical, environmental, and population-based drivers of Mycobacterium tuberculosis (Mtb) transmission in HIV endemic settings.
Description: Unacceptable levels of M. tuberculosis transmission are noted in high-burden settings and a renewed focus on reducing person to person transmission between the infected person (Transmitter) and others in shared air spaces (Recipient Cluster Chains) in these communities. This initiative will provide an improved understanding of where and when transmission occurs, the transmissibility of M. tuberculosis strains especially drug resistant ones, and the complex effect of HIV and antiretrovirals. This initiative will support multidisciplinary research studies of members of the Transmitter-Recipient Cluster Chains (TRCCs) that characterize host/pathogen/microenvironment interactions resulting in Mtb transmission in HIV-endemic settings. With improved knowledge of these interactions, novel approaches for preventing new TB infections and disease in the context of HIV infection could be developed or existing interventional strategies may be improved and adapted for a broad scale-up.
Research will be supported to characterize TB transmission events within the TRCC in HIV-endemic settings specifically in terms of:
- Aerobiology: Studies elucidating the infectious aerosol microenvironment and overall environmental aspects that promote transmission.
- Host factors: Studies may include identification of biomarkers of recent TB exposure/infection as well as underlying genetic or epigenetic factors and related regulatory genes and signaling pathways that play a role in changes in host responses that may determine transmission.
- Characteristics or subpopulations of Mtb strains, including drug resistant strains, that facilitate efficient transmission (for transmitters and for those becoming infected).
- Role of HIV in enhancing transmission (both for effects on the transmitters (e.g., aerosol infectious loads) and those at risk of becoming infected and effects of antiretroviral therapy.
- Studies of potential new interventions to decrease human-to-human transmission. Systemic chemoprophylaxis and host-directed therapeutic agents or vaccines are not included in this funding opportunity announcement. Studies of nosocomial transmission and high-risk groups (e.g., healthcare workers) will be encouraged.
The areas below are not responsive to this funding opportunity:
- Research proposals involving animal studies.
- Trials of systemic chemoprophylaxis, host-directed therapeutic agents, or vaccines primarily intended to prevent progression from latent infection to active disease.
For the published request for applications, see the December 4, 2017 Guide announcement, Understanding Immunopathogenesis of Tuberculosis in HIV-1 Infected and Exposed Children (R01 Clinical Trial Not Allowed).
For the published program announcement with special receipt, referral, and/or review considerations, see the April 20, 2018 Guide announcement, Harnessing Big Data to Halt HIV (R01 Clinical Trial Optional).
For the published program announcement, see the June 6, 2017 Guide announcement, Imaging the Persistent HIV Reservoir (R01).
For the published program announcement, see the June 7, 2017 Guide announcement, Optimizing HIV Phylodynamics to Target and Interrogate Clusters (OPTICS) (R21).