Delivering Therapeutics to Residual Active HIV Reservoirs (R01)
Grant Amount: NIAID intends to commit up to $2.42 million in FY 2014; NIMH intends to commit up to $500,000 in FY 2014 for studies focused on the central nervous system compartment.
The purpose of this FOA is to solicit new ideas for eliminating residual reservoirs of HIV that persist in individuals despite long-term suppression of plasma viremia by traditional antiretroviral therapy. Specifically, the research objective is to develop innovative strategies for improved delivery of antiretroviral drugs and other anti-HIV agents to specific cell types or tissue compartments that serve as persistent HIV-producing reservoirs. The majority of research on HIV persistence to date has focused on studies of latently infected resting CD4 T cells that do not actively produce virus. Indeed, most drug intensification and single-genome analysis studies of residual virus have not demonstrated evidence of ongoing viral replication or evolution in the plasma of individuals on optimally suppressive antiretroviral therapy. Nonetheless, emerging evidence suggests that it may be possible for cells in tissues such as the gut and lymph nodes to continue to produce low levels of HIV and, perhaps, to transmit virus from cell-to-cell at a low rate. This could potentially serve to re-seed the reservoir of persistent HIV. Continued virus production and infection could also lead to inflammation, which may play a role in maintaining the persistent reservoir of HIV. This lack of control of virus production and infection could, in part, be due to reduced concentrations of antiretrovirals in cells within specific tissue compartments.
Applications in response to this FOA should propose research to better understand the nature of the persistently active reservoir of HIV and to test innovative approaches to eliminate this reservoir. In addition to studies involving human subjects, investigators may also employ an animal model, such as humanized mice or non-human primates, to assess the effect of their proposed strategy on residual reservoirs of persistent HIV/SIV production in the context of optimized antiretroviral therapy. Therapeutics to be employed may include traditional small molecule inhibitors, as well as new classes of experimental therapeutics. Strategies may include the use of novel formulations or delivery methods, the use of therapeutics that concentrate in specific tissues or cell types associated with HIV reservoirs, or the rational design of new drug regimens based on pharmacology in specific tissues or cell types that serve as HIV reservoirs.
National Institute of Allergy and Infectious Diseases Division of AIDS US Department of Health and Human Services Public Health Services National Institutes of Health National Institute of Mental Health
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
Award Amount Notes
NIAID intends to commit up to $2.42 million in FY 2014. NIMH intends to commit up to $500,000 in FY 2014 for studies focused on the central nervous system compartment.
Letter of Intent Date
Application Due Date
Project Start Date
Grants.gov Customer Support , Phone: (800) 518-4726
Antiretroviral Drugs Medical Treatments and Therapies 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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