Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

Nat Commun. 2022 Oct 29;13(1):6473. doi: 10.1038/s41467-022-34171-2.

Abstract

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • CD8-Positive T-Lymphocytes
  • HIV Antibodies
  • HIV Infections*
  • HIV-1*
  • Humans
  • Interferon-gamma
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome*
  • Simian Immunodeficiency Virus*

Substances

  • Broadly Neutralizing Antibodies
  • Interferon-gamma
  • HIV Antibodies
  • Antibodies, Neutralizing