# Delaney AIDS Research Enterprise to Cure HIV

> **NIH NIH UM1** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $5,544,984

## Abstract

PROJECT SUMMARY/ABSTRACT
The mission of the DARE Collaboratory is to harness the power of the adaptive immune system to reduce the
size of the reservoir during antiretroviral therapy (ART) and to control any residual virus after ART is
interrupted. Our overall hypothesis is that that durable remission of HIV infection will require a robust immune
response that is persistent and functional. Moreover, these responses need to be in the right place at the right
time. We propose four highly linked research foci aimed at reaching these goals. We will define the role of
putative immune-privileged sanctuaries that enable SIV/HIV to persist during ART and use the monkey model
to develop therapies to breach these sanctuaries (Initial Research Foci 1, IRF1). We will characterize the
distribution on replication-competent virus in lymphoid tissues of ART-suppressed adults and develop PET
imaging modalities to quantify this reservoir (IRF2). We will define the role of immune checkpoints (PD-1,
others) and their blockade on T cell function in monkeys and people (IRF3). Finally, we will define the safety,
immunogenicity, and anti-HIV effectiveness of a human CMV (HCMV) vectored HIV vaccine in HIV-infected
adults on ART (IRF4). All four initial research foci are linked by their shared goal to understand how best to
quantify, reduce, and control HIV in the human lymphoid system. We anticipate meeting the following
milestones and deliverables: (1) definition of the replication-competent reservoir in lymphoid tissues from SIV-
infected monkeys and HIV-infected humans on suppressive ART, (2) determination of whether B follicles serve
as a immunologic sanctuary for infected CD4+ TFH and, if so, whether B follicular depletion reduces the size of
the reservoir, (3) determination of the characteristics of virus-specific CD8+ T cell responses that have optimal
activity for reservoir reduction and/or post-ART viral control, (4) determination if the tissue reservoir can be
measured by radiolabeled tracers and PET scanning, (5) identification of the optimal combination of immune
checkpoint blockers that enhance T-cell function and/or reverse HIV latency, (6) definition of the safety and
immunogenicity of immune checkpoint blockers in treated SIV and HIV disease, (7) determination of the safety
and immunogenicity of the HCMV/HIV vaccine in treated HIV disease, and (8) determination if B cell disruption
and/or immune checkpoint blockade might be necessary for this vaccine (or other comparable interventions) to
achieve reservoir reduction and/or durable remission. Our work will set the stage for a future proof-of-concept
clinical trial of the HCMV/HIV vector in antiretroviral-treated individuals, either alone or in combination with B
cell follicle disruption and/or immune checkpoint blockade.

## Key facts

- **NIH application ID:** 9978687
- **Project number:** 5UM1AI126611-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** STEVEN Grant DEEKS
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $5,544,984
- **Award type:** 5
- **Project period:** 2016-07-14 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978687

## Citation

> US National Institutes of Health, RePORTER application 9978687, Delaney AIDS Research Enterprise to Cure HIV (5UM1AI126611-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9978687. Licensed CC0.

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