PT  - JOURNAL ARTICLE
AU  - Jason T. Weinfurter
AU  - Saritha S. D’Souza
AU  - Lea M. Matschke
AU  - Sarah Bennett
AU  - Laurel E. Kelnhofer-Millevolte
AU  - Kran Suknuntha
AU  - Akhilesh Kumar
AU  - Jennifer Coonen
AU  - Christian M. Capitini
AU  - Peiman Hematti
AU  - Thaddeus G. Golos
AU  - Igor I. Slukvin
AU  - Matthew R. Reynolds
TI  - MHC-matched allogeneic bone marrow transplant fails to eliminate SHIV-infected cells from ART-suppressed Mauritian cynomolgus macaques
AID  - 10.1101/2021.04.16.440168
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.16.440168
4099  - http://biorxiv.org/content/early/2021/04/16/2021.04.16.440168.short
4100  - http://biorxiv.org/content/early/2021/04/16/2021.04.16.440168.full
AB  - Objective Allogeneic hematopoietic stem cell transplants (allo-HSCTs) in antiretroviral therapy (ART) suppressed individuals can significantly reduce human immunodeficiency virus (HIV) latent reservoirs and lead to prolonged ART-free remission. The mechanisms reducing the reservoir size are not fully understood but may include pre-transplant conditioning regimens, ART-mediated protection of donor cells, and graft-versus-host responses.Design We modeled allo-HSCT in four ART-suppressed simian-human immunodeficiency virus (SHIV)-infected Mauritian cynomolgus macaques (MCMs) to examine the role of transplant-mediated factors in eliminating SHIV latently infected cells.Methods SHIV-infected MCMs started ART 6-16 weeks post-infection. After 3-6 weeks on ART, the MCMs received myeloablative conditioning and MHC-matched bone marrow depleted of α/β T cells. The MCMs were treated with GvH disease (GvHD) prophylaxis consisting of cyclophosphamide and tacrolimus and maintained daily ART post-transplant. One MCM was removed from ART 74 days post-transplant, while the remaining three MCMs continued ART until their necropsies. Viral reservoirs were measured in the peripheral blood and lymph nodes pre- and post-transplant and tissues at necropsy.Results The treatment regimen induced profound lymphocyte depletion without causing severe GvHD, producing undetectable viral loads post-transplant. However, SHIV-harboring cells persisted in lymphoid and non-lymphoid tissues, resulting in a rapid viral rebound in the ART-withdrawn MCM.Conclusions Our results indicate that myeloablative conditioning and maintaining ART through the peri-transplant period alone are insufficient for eradicating latent reservoirs early after transplant. They also suggest that GvH responses mediated by α/β T cells are likely necessary to kill HIV latently infected cells following allo-HSCTs.Competing Interest StatementThe authors have declared no competing interest.