Evaluation of HIV-specific T-cell responses in HIV-infected older patients with controlled viremia on long-term antiretroviral therapy

PLoS One. 2020 Sep 17;15(9):e0236320. doi: 10.1371/journal.pone.0236320. eCollection 2020.

Abstract

HIV-infected older individuals may have a diminished immune response because of exhaustion/immune aging of T-cells. Therefore, we have investigated HIV-specific CD4 and CD8 T-cell responses in 100 HIV-infected patients (HIV+) who have aged on long-term antiretroviral therapy (ART) and achieved controlled viremia (mostly undetectable viral load; 92 patients with <20 to <40 HIV RNA copies/mL and 8 <60 to <100) and improved CD4 T-cell counts. We show that the median frequencies of HIV-specific CD4+ and CD8+ IFN-γ T-cells were higher in HIV+ than uninfected individuals (HIV-), including increasing levels of IFN-γproduced by CD4+ T-cells and decreasing levels by CD8+ T-cells with increasing CD4 T-cell counts in HIV+. No correlation was found between T-cell responses and varying levels of undetectable viremia. HIV-specific TNF-α made by CD8+ T-cells was higher in HIV+ than HIV-, including decreasing levels with increasing CD4 T-cell counts in HIV+. Furthermore, the CD8+ T-cell mediators, CD107a and Granzyme-B, were higher in HIV+ than HIV-, and decreased with increasing CD4 T-cell counts in HIV+. Remarkably, HIV-specific CD8 T-cells produced decreasing levels of IFN-γwith increasing age of HIV+, including decreased levels of CD107a and Granzyme-B in older HIV+. However, HIV-specific CD8+ T-cells produced increasing levels of TNF-α with increasing age of the HIV+, suggesting continued inflammation. In conclusion, HIV+ with controlled viremia on long-term ART and with higher CD4 T-cell counts showed reduced HIV-specific CD8 T-cell responses as compared to those with lower CD4 T-cell counts, and older HIV+ exhibited decreasing levels of CD8 T-cell responses with increasing age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Retroviral Agents / administration & dosage
  • Anti-Retroviral Agents / therapeutic use*
  • CD4-CD8 Ratio
  • Female
  • Granzymes / genetics
  • Granzymes / metabolism
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Lysosomal-Associated Membrane Protein 1 / genetics
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Viremia / blood*
  • Viremia / drug therapy

Substances

  • Anti-Retroviral Agents
  • Lysosomal-Associated Membrane Protein 1
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Granzymes

Grants and funding

The work presented in this manuscript was supported by a grant to NA from the Arizona Biomedical Research Commission, Arizona Department of Health Services (ADHS14-082984). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.