• Nathan W Cummins, Stacey Rizza, Mark R Litzow, Stephane Hua, Guinevere Q Lee, Kevin Einkauf, Tae-Wook Chun, Frank Rhame, Jason V Baker, Michael P Busch, Nicolas Chomont, Patrick G Dean, Rémi Fromentin, Ashley T Haase, Dylan Hampton, Sheila M Keating, Steven M Lada, Tzong-Hae Lee, Sekar Natesampillai, Douglas D Richman, Timothy W Schacker, Stephen Wietgrefe, Xu G Yu, Joseph D Yao, John Zeuli, Mathias Lichterfeld, and Andrew D Badley.
• Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
• PLoS Med. 2017 Nov 1; 14 (11): e1002461e1002461.

BackgroundNotwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia.Methods And FindingsWe prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case.Conclusionsallo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

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