Innovative Assays to Quantify the Latent HIV Reservoir (R21)
Grant Amount: NIAID intends to commit $1.125 million yearly to make 4-6 awards.
The purpose of this Funding Opportunity Announcement (FOA) is to support research on new or improved methods for quantifying latently infected cells in HIV-positive individuals on effective antiretroviral therapy. Quantifying latent HIV reservoirs is critical to evaluating strategies to cure HIV infection in vivo. The current gold-standard method involves a limiting dilution viral outgrowth assay that is slow, resource-intensive, and relatively imprecise. A molecular assay to accurately detect replication-competent provirus, or a viral outgrowth assay with improved efficiency, would facilitate proof-of-concept studies for curing HIV infection.
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).
Examples of research that would fit within the scope of this FOA include, but are not limited to the following:
modifications to the current viral outgrowth assay to improve throughput, cost, precision, or accuracy; technologies to adapt the viral outgrowth assay to a miniaturized, high-throughput platform; the automation of steps in the viral outgrowth assay protocol; the use of advanced detection technologies to quantify latent HIV; and the development of a molecular assay that could serve as a surrogate for the viral outgrowth assay in quantifying replication-competent latent HIV reservoirs.
National Institute of Allergy and Infectious Diseases Division of Intramural Research
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
4 - 6 awards
Award Amount Notes
NIAID intends to commit $1.125 million yearly to make 4-6 awards.
Antiretroviral Drugs HIV Positive Persons Research Programs
Applicants can access 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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