HIV envelope antibodies and TLR7 agonist partially prevent viral rebound in chronically SHIV-infected monkeys

PLoS Pathog. 2022 Apr 22;18(4):e1010467. doi: 10.1371/journal.ppat.1010467. eCollection 2022 Apr.

Abstract

A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown delay or prevention of viral rebound following antiretroviral therapy (ART) discontinuation in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques. In these prior studies, ART was initiated early during acute infection, which limited the size and diversity of the viral reservoir. Here we evaluated in SHIV-infected rhesus macaques that did not initiate ART until 1 year into chronic infection whether the TLR7 agonist vesatolimod in combination with the bNAb PGT121, formatted either as a human IgG1, an effector enhanced IgG1, or an anti-CD3 bispecific antibody, would delay or prevent viral rebound following ART discontinuation. We found that all 3 antibody formats in combination with vesatolimod were able to prevent viral rebound following ART discontinuation in a subset of animals. These data indicate that a TLR7 agonist combined with antibodies may be a promising strategy to achieve long-term ART-free HIV remission in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Retroviral Agents / pharmacology
  • Anti-Retroviral Agents / therapeutic use
  • Broadly Neutralizing Antibodies
  • HIV Antibodies / therapeutic use
  • HIV Infections*
  • HIV-1*
  • Immunoglobulin G
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome*
  • Simian Immunodeficiency Virus*
  • Toll-Like Receptor 7 / agonists
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • Immunoglobulin G
  • Toll-Like Receptor 7

Grants and funding

The study was funded by Gilead Sciences (D.H.B.). The funders were co-authors and participated in study design, data analysis, and preparation of the manuscript. They did not influence data collection or decision to publish.