# Optimizing eCD4-Ig for eradication and a functional cure

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $24,596

## Abstract

PROJECT SUMMARY
One strategy for eradicating the HIV-1 viral reservoir combines a means of activating viral gene
expression in latently infected T cells (a ‘kick’) with a way to eliminate these activated cells (a ‘kill’). The
TLR7 agonist GS-9620 is a safe, well tolerated latency reversing agent that indirectly induces latently
infected T cells to produce virus. Preliminary data indicates that it can partially reduce, or in some
cases perhaps completely eliminate, the SIV reservoir in rhesus macaques. eCD4-Ig is an antibody-
like entry inhibitor with unmatched breadth and very potent neutralizing and antibody-dependent cell-
mediated cytotoxicity (ADCC) activities against HIV-1, HIV-2 and SIV. Moreover, it can protect
macaques against from repeated high-dose challenges with two divergent viruses – SIVmac239 and
SHIV-AD8. Finally a single dose of an IgG1 form of human eCD4-Ig protein can suppress infection in
macaques by 2.5 logs without evidence of viral escape. eCD4-Ig’s potent neutralization and ADCC
activities, and its exceptional breadth, suggest that it may uniquely overcome the diversity of the viral
reservoir and facilitate the elimination of most reactivated cells.
Accordingly, we will test the hypothesis that the effector functions of eCD4-Ig can accelerate reduction
of the latent reservoir observed in GS-9620-treated macaques. To do so, we will first optimize the half-
life, immunogenicity, neutralization potency, and ADCC activities of eCD4-Ig. We will then optimize the
schedule, dosing, and route of administration of GS-9620, and establish the relationship between GS-
9620-induced virus ‘blips’ and reservoir reduction. Finally, we will compare GS-9620, eCD4-Ig, and
both therapies combined, for their abilities to reduce the size of the latent reservoir and/or establish a
stable state of virologic control. If successful, these studies will lay a foundation for future human
clinical trials combining GS-9620 and eCD4-Ig.

## Key facts

- **NIH application ID:** 10591670
- **Project number:** 6R01AI129868-06
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Michael R. Farzan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $24,596
- **Award type:** 6
- **Project period:** 2017-08-16 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10591670

## Citation

> US National Institutes of Health, RePORTER application 10591670, Optimizing eCD4-Ig for eradication and a functional cure (6R01AI129868-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10591670. Licensed CC0.

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