# 3BNC117 and 10-1074 to suppress HIV-1 replication and reduce the reservoir

> **NIH NIH U01** · ROCKEFELLER UNIVERSITY · 2020 · $814,897

## Abstract

Project Summary
Combination antiretroviral therapy (ART) is highly successful in suppressing viral replication and preventing
disease progression, however it cannot eradicate HIV-1 infection, and it does not accelerate the elimination of
infected cells. HIV-1 persists in a latent state as integrated proviruses in resting memory CD4+ T cells that are
not accessible to ART. Several eradication strategies are currently being evaluated, and broadly neutralizing
antibodies (bNAbs) represent a promising new modality, particularly if coupled with latency reversing agents.
Antibodies differ from ART in that they can recruit immune effector functions through their Fc domains to
accelerate clearance of viruses and infected cells. In addition, immune complexes are potent immunogens that
can foster development of host immune responses. Passive administration of earlier anti-HIV-1 bNAbs has
been evaluated in humans and found to be generally safe and well tolerated. While these first generation
neutralizing antibodies were largely ineffective in preclinical and clinical settings, selected newer generation
bNAbs can prevent infection and suppress active infection in humanized mice (hu-mice) and non-human
primates (NHP). 3BNC117 and 10-1074 are two of most potent broadly neutralizing antibodies currently
available. 3BNC117 targets the CD4 binding site and 10-1074 targets the base of the V3 loop of HIV-1 gp120.
In phase 1 clinical studies, 3BNC117 and 10-1074 have been generally safe to date. A single infusion of
3BNC117 suppressed HIV-1 viremia by an average of 1.48 log copies/ml, while 10-1074 suppressed HIV-1
viremia by an average of 1.34 copies/ml when dosed at 30 mg/kg. When evaluated in ART-treated individuals
during an analytical interruption of ART (ATI), 3BNC117 effectively delayed rebound of antibody sensitive
viruses from the HIV-1 reservoir. Similar to preclinical findings, selection of resistant viral strains occurred
when either antibody was administered alone. The combination of 3BNC117 and 10-1074 have additive effects
and provide broader coverage of viral strains. We now propose to study whether the administration of
3BNC117 and 10-1074 can suppress replication and reduce the reservoir by engaging the host immune
system. The envisioned clinical trial is a phase I, open label, randomized study to evaluate the antiretroviral
activity of 6 monthly infusions of 3BNC117 and 10-1074 to HIV-infected subjects who have achieved viral
suppression with ART alone, in the presence or absence of ART. We will evaluate the reservoir by quantitative
and qualitative methods to determine the genetic composition of the replication-competent viral reservoir. In
addition, we will evaluate if 3BNC117 and 10-1074 modulate HIV-1-specific immune responses.

## Key facts

- **NIH application ID:** 9897465
- **Project number:** 5U01AI129825-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Marina Caskey
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $814,897
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897465

## Citation

> US National Institutes of Health, RePORTER application 9897465, 3BNC117 and 10-1074 to suppress HIV-1 replication and reduce the reservoir (5U01AI129825-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897465. Licensed CC0.

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