Innovative Assays to Quantify the Latent HIV Reservoir (R01)
Grant Amount: NIAID intends to commit $1.3 million in FY 2015 to fund 2-4 awards.
The goal of this FOA is to support research on the development of innovative high-throughput approaches for quantifying the very low levels of latently infected cells that persist in HIV-positive individuals on HAART. Ideally, a new assay is needed that specifically quantifies resting CD4 memory T cells that contain integrated, replication-competent provirus. The key challenges to be overcome are: (1) the low frequency of these cells (only about 1 in 106 resting cells contains functional provirus), (2) the lack of cell surface markers distinguishing latently infected cells from uninfected cells, and (3) the abundance of defective HIV DNA (only about 1% of HIV DNA in resting CD4 T cells represents replication-competent provirus).
One example of a new approach would be to develop a molecular assay that quantifies integrated, full-length provirus, coupled with sequence analysis to predict replication competence. Such an assay could potentially have higher throughput, faster turnaround, lower cost, and greater reproducibility than the Q-VOA.
Other approaches that quantify latent HIV reservoirs are also of interest if they address the three key challenges listed above and correlate with the level of replication-competent virus present in latently infected cells as determined by Q-VOA.
Improvements to the Q-VOA are also needed and are supported under this FOA. An example of an approach to improve the Q-VOA would be miniaturization of the assay to allow high-throughput analysis of single cells. Another approach might employ highly sensitive indicator cells to eliminate the need for extended co-culture with donor PBMC feeder cells and to provide a more efficient, quantitative endpoint.
Applications that leverage inter-disciplinary collaborations to apply cutting-edge technologies to address these challenges are especially encouraged. It is highly recommended that applications propose to validate the approach by comparison to the existing Q-VOA. While transformed cell lines and primary cell models for latent HIV may be used for initial assay development work, it is imperative that validation studies be extended to include the use of latently infected cells from HIV-positive individuals on optimized HAART. Applications proposing to develop assays for measuring the latent viral reservoir in animal models of HIV/SIV in the context of suppressive HAART regimens will also be considered responsive to the FOA.
Through various sponsored grants and contracts, the NIAID can provide to the research community limited resources in the form of Q-VOA services and access to latently infected resting T cells from HIV-positive individuals. Applicants may inquire about these resources by contacting the Scientific/Research Contact listed in Section VII. Agency Contact(s) of this FOA.
National Institute of Allergy and Infectious Diseases Division of AIDS
City Agencies Colleges/Universities Commercial Organizations Community Based Organizations County Agencies Educational Organizations/Institutions Federal Government Agencies International Agencies IRS 501 (c)(3) Organizations Nonprofit Organizations Religious Organizations Schools State Agencies Tribal Organizations
Number of Awards Given
2 to 4 awards
Award Amount Notes
NIAID intends to commit $1.3 million in FY 2015 to fund 2-4 awards.
Antiretroviral Drugs HIV Positive Persons Research Programs
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerB.pdf), except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
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