HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

Nat Med. 2017 May;23(5):638-643. doi: 10.1038/nm.4319. Epub 2017 Apr 17.


Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (∼33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.

MeSH terms

  • Animals
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Bone Marrow
  • DNA, Viral
  • Electrophoresis, Gel, Pulsed-Field
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunohistochemistry
  • Lactones
  • Leukocytes, Mononuclear
  • Liver
  • Macrophages / virology*
  • Macrophages, Alveolar / virology
  • Mice
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Phenols
  • RNA, Viral
  • Spleen
  • T-Lymphocytes
  • Viral Load
  • Virus Latency
  • Virus Replication


  • Anti-HIV Agents
  • DNA, Viral
  • Lactones
  • NR4A2 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Phenols
  • RNA, Viral
  • NG 011