Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study

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. RichmanTimothy W. Schacker, Stephen Wietgrefe, Xu G. Yu, Joseph D. Yao, John Zeuli, Mathias Lichterfeld, Andrew D. Badley

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23 Scopus citations

Abstract

Background: Notwithstanding 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 findings: We 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. Conclusions: allo-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.

Original languageEnglish (US)
Article numbere1002461
JournalPLoS Medicine
Volume14
Issue number11
DOIs
StatePublished - Nov 2017

Bibliographical note

Funding Information:
ADB is supported by NIH grants AI110173 and AI120698. ML is supported by NIH grants AI098487, AI106468, AI114235, AI117841, AI120008, AI124776. XGY is supported by NIH grants AI116228, AI078799, HL134539. DDR is supported by the Collaboratory for AIDS Research on Eradication (CARE; U19 AI096113 and 1UM1AI126619), the UCSD CFAR (AI306214), the Department of Veterans Affairs, and the James B. Pendleton Charitable Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We greatly appreciate and acknowledge our patient described herein for volunteering his time, for donating numerous samples that allowed the detailed studies to be performed, and for consenting to this publication. We also acknowledge the clinical teams that cared for our patient before, during, and following his transplant. We would like to thank Dr. Steven Deeks for his invaluable advice during the conduct of this study.

Publisher Copyright:
© 2017 Public Library of Science. All Rights Reserved.

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