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

2018; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41467-018-06736-7

2041-1723

Lucrezia Colonna, Christopher W. Peterson, John B. Schell, Judith Carlson, Victor Tkachev, Melanie Brown, Alison Yu, Sowmya Reddy, Willi M. Obenza, Veronica Nelson, Patricia Polacino, Heather Mack, Shiu-Lok Hu, Katie Zeleski, Michelle Hoffman, Joe Olvera, Scott N. Furlan, Hengqi Zheng, Agne Taraseviciute, Daniel J. Hunt, Kayla Betz, Jennifer Lane, Keith Vogel, Charlotte E. Hotchkiss, Cassie Moats, Audrey Baldessari, Robert D. Murnane, Christopher N. English, Cliff A. Astley, Solomon Wangari, Brian Agricola, Joel Ahrens, Naoto Iwayama, Andrew P. May, Laurence Stensland, Meei‐Li Huang, Keith R. Jerome, Hans‐Peter Kiem, Leslie S. Kean,

Immunotherapy and Immune Responses

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.