Clonal expansion of SIV-infected cells in macaques on antiretroviral therapy is similar to that of HIV-infected cells in humans

PLoS Pathog. 2019 Jul 10;15(7):e1007869. doi: 10.1371/journal.ppat.1007869. eCollection 2019 Jul.


Clonal expansion of HIV infected cells plays an important role in the formation and persistence of the reservoir that allows the virus to persist, in DNA form, despite effective antiretroviral therapy. We used integration site analysis to ask if there is a similar clonal expansion of SIV infected cells in macaques. We show that the distribution of HIV and SIV integration sites in vitro is similar and that both viruses preferentially integrate in many of the same genes. We obtained approximately 8000 integration sites from blood samples taken from SIV-infected macaques prior to the initiation of ART, and from blood, spleen, and lymph node samples taken at necropsy. Seven clones were identified in the pre-ART samples; one persisted for a year on ART. An additional 100 clones were found only in on-ART samples; a number of these clones were found in more than one tissue. The timing and extent of clonal expansion of SIV-infected cells in macaques and HIV-infected cells in humans is quite similar. This suggests that SIV-infected macaques represent a useful model of the clonal expansion of HIV infected cells in humans that can be used to evaluate strategies intended to control or eradicate the viral reservoir.

Publication types

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

MeSH terms

  • Animals
  • Anti-Retroviral Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / virology
  • Disease Reservoirs / virology
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / virology*
  • Host Microbial Interactions / drug effects
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / physiology
  • Humans
  • In Vitro Techniques
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / pathology
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / pathogenicity
  • Viral Load / drug effects
  • Virus Integration / genetics
  • Virus Integration / physiology
  • Virus Replication / drug effects


  • Anti-Retroviral Agents