Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

Nat Commun. 2018 Oct 25;9(1):4438. doi: 10.1038/s41467-018-06736-7.


Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.

Publication types

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

MeSH terms

  • Animals
  • Antiretroviral Therapy, Highly Active
  • CD8-Positive T-Lymphocytes / immunology
  • DNA, Viral / metabolism
  • Disease Reservoirs / virology*
  • Hematopoietic Stem Cell Transplantation*
  • Macaca mulatta
  • Major Histocompatibility Complex*
  • RNA, Viral / metabolism
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / physiology*
  • Transplantation, Haploidentical*
  • Transplantation, Homologous


  • DNA, Viral
  • RNA, Viral