UM1AI164560
Cooperative Agreement
Overview
Grant Description
Delaney AIDS Research Enterprise to Cure HIV - Project Summary/Abstract
The goals of the DARE Collaboratory are to develop a viable combination regimen that reduces the rebound-competent HIV/SIV reservoir during antiretroviral therapy (ART) and/or induces durable control of HIV/SIV in the absence of therapy. Our proposed work is based on two observations made by our group.
First, we found that virus-specific CD8+ T cells contribute to control of the virus at steady-state. However, these cells have limited effect during and immediately post-ART. We believe, and will seek to prove, that effective remission strategies will require organization of a robust innate and adaptive immune response during the earliest stages of virus rebound. This will effectively intercept and suppress viral rebound prior to the massive systemic growth of SIV/HIV that overwhelms, damages, and/or evades the immune system.
Second, we and others have found that despite virus expression during ART (either naturally or in response to a latency reversal agent), the frequency of infected cells remains stable. We have found that infected cells are relatively resistant to cell death programs. We will develop therapies that render these cells susceptible to host-mediated clearance mechanisms, thus resulting in their reduction and perhaps elimination.
To achieve our goals, we will:
1. Characterize transcriptionally active cells and proliferating infected cells in people, focusing on identifying mechanisms for persistence.
2. Define the earliest immunologic and virologic events post-interruption of ART in people, focusing on post-treatment controllers.
3. Develop a combination regimen in non-human primates (NHPs) that targets the reactivating virus during the immediate post-ART period and results in sustained control at set-point.
4. Develop therapies in vitro and in animal models that render the reservoir more susceptible to death through the activation of intrinsic (cellular) and/or extrinsic (virus-specific) pro-apoptotic pathways.
This work will leverage our deep investment in:
1. The optimization of the SIV NHP model and a humanized mouse model, both developed specifically to support the types of studies we will pursue.
2. The development of a robust clinical cohort (SCOPE) designed to support intensive, biologic studies of people living with HIV (PWH).
3. The implementation and conduct of several clinical trials designed in part to test our hypotheses in people, from which samples will be made available to our team for ex vivo studies.
We anticipate meeting the following milestones and deliverables:
1. Definition of the active reservoir in lymphoid tissues from SIV-infected monkeys and HIV-infected humans on effective ART.
2. Determination of whether reservoir cells are resistant to intrinsic and extrinsic cell killing.
3. Development of a viable and translatable remission strategy in NHPs.
4. Identification and pre-clinical development of interventions aimed at enhancing cell death, either by making cells more susceptible to cell death and/or by optimizing the efficacy of the virus-specific T cell response.
The goals of the DARE Collaboratory are to develop a viable combination regimen that reduces the rebound-competent HIV/SIV reservoir during antiretroviral therapy (ART) and/or induces durable control of HIV/SIV in the absence of therapy. Our proposed work is based on two observations made by our group.
First, we found that virus-specific CD8+ T cells contribute to control of the virus at steady-state. However, these cells have limited effect during and immediately post-ART. We believe, and will seek to prove, that effective remission strategies will require organization of a robust innate and adaptive immune response during the earliest stages of virus rebound. This will effectively intercept and suppress viral rebound prior to the massive systemic growth of SIV/HIV that overwhelms, damages, and/or evades the immune system.
Second, we and others have found that despite virus expression during ART (either naturally or in response to a latency reversal agent), the frequency of infected cells remains stable. We have found that infected cells are relatively resistant to cell death programs. We will develop therapies that render these cells susceptible to host-mediated clearance mechanisms, thus resulting in their reduction and perhaps elimination.
To achieve our goals, we will:
1. Characterize transcriptionally active cells and proliferating infected cells in people, focusing on identifying mechanisms for persistence.
2. Define the earliest immunologic and virologic events post-interruption of ART in people, focusing on post-treatment controllers.
3. Develop a combination regimen in non-human primates (NHPs) that targets the reactivating virus during the immediate post-ART period and results in sustained control at set-point.
4. Develop therapies in vitro and in animal models that render the reservoir more susceptible to death through the activation of intrinsic (cellular) and/or extrinsic (virus-specific) pro-apoptotic pathways.
This work will leverage our deep investment in:
1. The optimization of the SIV NHP model and a humanized mouse model, both developed specifically to support the types of studies we will pursue.
2. The development of a robust clinical cohort (SCOPE) designed to support intensive, biologic studies of people living with HIV (PWH).
3. The implementation and conduct of several clinical trials designed in part to test our hypotheses in people, from which samples will be made available to our team for ex vivo studies.
We anticipate meeting the following milestones and deliverables:
1. Definition of the active reservoir in lymphoid tissues from SIV-infected monkeys and HIV-infected humans on effective ART.
2. Determination of whether reservoir cells are resistant to intrinsic and extrinsic cell killing.
3. Development of a viable and translatable remission strategy in NHPs.
4. Identification and pre-clinical development of interventions aimed at enhancing cell death, either by making cells more susceptible to cell death and/or by optimizing the efficacy of the virus-specific T cell response.
Funding Goals
TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.
Grant Program (CFDA)
Place of Performance
San Francisco,
California
941102859
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 445% from $4,946,032 to $26,967,938.
San Francisco Regents Of The University Of California was awarded
DARE HIV Cure: Remission Strategy & Reservoir Reduction
Cooperative Agreement UM1AI164560
worth $26,967,938
from the National Institute of Diabetes and Digestive and Kidney Diseases in August 2021 with work to be completed primarily in San Francisco California United States.
The grant
has a duration of 4 years 8 months and
was awarded through assistance program 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research.
The Cooperative Agreement was awarded through grant opportunity Martin Delaney Collaboratories for HIV Cure Research (UM1 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 7/21/25
Period of Performance
8/16/21
Start Date
4/30/26
End Date
Funding Split
$27.0M
Federal Obligation
$0.0
Non-Federal Obligation
$27.0M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for UM1AI164560
Transaction History
Modifications to UM1AI164560
Additional Detail
Award ID FAIN
UM1AI164560
SAI Number
UM1AI164560-370674852
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Funding Office
75NK00 NIH National Institute of Diabetes and Digestive and Kidney Diseases
Awardee UEI
KMH5K9V7S518
Awardee CAGE
4B560
Performance District
CA-11
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute of Allergy and Infectious Diseases, National Institutes of Health, Health and Human Services (075-0885) | Health research and training | Grants, subsidies, and contributions (41.0) | $9,567,990 | 88% |
| National Institute on Drug Abuse, National Institutes of Health, Health and Human Services (075-0893) | Health research and training | Grants, subsidies, and contributions (41.0) | $416,666 | 4% |
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $333,334 | 3% |
| National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Health and Human Services (075-0884) | Health research and training | Grants, subsidies, and contributions (41.0) | $333,334 | 3% |
Modified: 7/21/25