CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy

Immunity. 2016 Sep 20;45(3):656-668. doi: 10.1016/j.immuni.2016.08.018.


Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Retroviral Agents / pharmacology*
  • Antibodies, Viral / immunology
  • Antiretroviral Therapy, Highly Active / methods
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Lymphocyte Depletion / methods
  • Macaca mulatta
  • Male
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / immunology*
  • Viral Load / drug effects
  • Viral Load / immunology
  • Viremia / drug therapy
  • Viremia / immunology
  • Viremia / virology
  • Virus Replication / drug effects
  • Virus Replication / immunology


  • Anti-Retroviral Agents
  • Antibodies, Viral