Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy

J Clin Invest. 2021 Mar 15;131(6):e142421. doi: 10.1172/JCI142421.


The effectiveness of virus-specific strategies, including administered HIV-specific mAbs, to target cells that persistently harbor latent, rebound-competent HIV genomes during combination antiretroviral therapy (cART) has been limited by inefficient induction of viral protein expression. To examine antibody-mediated viral reservoir targeting without a need for viral induction, we used an anti-CD4 mAb to deplete both infected and uninfected CD4+ T cells. Ten rhesus macaques infected with barcoded SIVmac239M received cART for 93 weeks starting 4 days after infection. During cART, 5 animals received 5 to 6 anti-CD4 antibody administrations and CD4+ T cell populations were then allowed 1 year on cART to recover. Despite profound CD4+ T cell depletion in blood and lymph nodes, time to viral rebound following cART cessation was not significantly delayed in anti-CD4-treated animals compared with controls. Viral reactivation rates, determined based on rebounding SIVmac239M clonotype proportions, also were not significantly different in CD4-depleted animals. Notably, antibody-mediated depletion was limited in rectal tissue and negligible in lymphoid follicles. These results suggest that, even if robust viral reactivation can be achieved, antibody-mediated viral reservoir depletion may be limited in key tissue sites.

Keywords: AIDS/HIV; T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-HIV Agents / administration & dosage
  • Anti-Retroviral Agents / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Viral / administration & dosage*
  • CD4 Antigens / antagonists & inhibitors
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Lymphocyte Depletion
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / virology
  • 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*
  • Simian Immunodeficiency Virus / physiology
  • Viral Load / drug effects
  • Viral Load / immunology
  • Virus Activation / drug effects
  • Virus Activation / immunology
  • Virus Replication / drug effects
  • Virus Replication / immunology


  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • CD4 Antigens