Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity

Nat Med. 2020 Feb;26(2):222-227. doi: 10.1038/s41591-019-0747-1. Epub 2020 Feb 3.

Abstract

Combination antiretroviral therapy (ART) is highly effective in controlling human immunodeficiency virus (HIV)-1 but requires lifelong medication due to the existence of a latent viral reservoir1,2. Potent broadly neutralizing antibodies (bNAbs) represent a potential alternative or adjuvant to ART. In addition to suppressing viremia, bNAbs may have T cell immunomodulatory effects as seen for other forms of immunotherapy3. However, this has not been established in individuals who are infected with HIV-1. Here, we document increased HIV-1 Gag-specific CD8+ T cell responses in the peripheral blood of all nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving bNAb therapy during ART interruption4. Increased CD4+ T cell responses were detected in eight individuals. The increased T cell responses were due both to newly detectable reactivity to HIV-1 Gag epitopes and the expansion of pre-existing measurable responses. These data demonstrate that bNAb therapy during ART interruption is associated with enhanced HIV-1-specific T cell responses. Whether these augmented T cell responses can contribute to bNAb-mediated viral control remains to be determined.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Epitopes / immunology
  • Female
  • Gene Products, gag / metabolism
  • HIV Antibodies / immunology*
  • HIV Infections / immunology*
  • HIV Infections / therapy*
  • HIV Infections / virology
  • HIV-1
  • Humans
  • Immune System
  • Immunotherapy / methods*
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Viremia

Substances

  • Antibodies, Neutralizing
  • Epitopes
  • Gene Products, gag
  • HIV Antibodies
  • Interferon-gamma