Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant

Maria Salgado, Mi Kwon, Cristina Gálvez, Jon Badiola, Monique Nijhuis, Alessandra Bandera, Pascual Balsalobre, Pilar Miralles, Ismael Buño, Carolina Martinez-Laperche, Cristina Vilaplana, Manuel Jurado, Bonaventura Clotet, Annemarie Wensing, Javier Martinez-Picado, Jose Luis Diez-Martin

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25 Citations (Scopus)

Abstract

© 2018 American College of Physicians. Background: The multifactorial mechanisms associated with radical reductions in HIV-1 reservoirs after allogeneic hematopoietic stem cell transplant (allo-HSCT), including a case of HIV cure, are not fully understood. Objective: To investigate the mechanism of HIV-1 eradication associated with allo-HSCT. Design: Nested case series within the IciStem observational cohort. Setting: Multicenter European study. Participants: 6 HIV-infected, antiretroviral-treated participants who survived more than 2 years after allo-HSCT with CCR5 wildtype donor cells. Measurements: HIV DNA analysis, HIV RNA analysis, and quantitative viral outgrowth assay were performed in blood, and HIV DNA was also measured in lymph nodes, ilea, bone marrow, and cerebrospinal fluid. A humanized mouse model was used for in vivo detection of the replication-competent blood cell reservoir. HIV-specific antibodies were measured in plasma. Results: Analysis of the viral reservoir showed that 5 of 6 participants had full donor chimera in T cells within the first year after transplant, undetectable proviral HIV DNA in blood and tissue, and undetectable replication-competent virus (<0.006 infectious unit per million cells). The only participant with detectable virus received cord blood stem cells with an antithymocyte globulin- containing conditioning regimen, did not develop graft-versushost disease, and had delayed complete standard chimerism in T cells (18 months) with mixed ultrasensitive chimera. Adoptive transfer of peripheral CD4+ T cells to immunosuppressed mice resulted in no viral rebound. HIV antibody levels decreased over time, with 1 case of seroreversion. Limitation: Few participants. Conclusion: Allo-HSCT resulted in a profound long-term reduction in the HIV reservoir. Such factors as stem cell source, conditioning, and a possible "graft-versus-HIV-reservoir" effect may have contributed. Understanding the mechanisms involved in HIV eradication after allo-HSCT can enable design of new curative strategies.
Original languageEnglish
Pages (from-to)674-683
JournalAnnals of Internal Medicine
Volume169
DOIs
Publication statusPublished - 20 Nov 2018

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    Salgado, M., Kwon, M., Gálvez, C., Badiola, J., Nijhuis, M., Bandera, A., Balsalobre, P., Miralles, P., Buño, I., Martinez-Laperche, C., Vilaplana, C., Jurado, M., Clotet, B., Wensing, A., Martinez-Picado, J., & Diez-Martin, J. L. (2018). Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant. Annals of Internal Medicine, 169, 674-683. https://doi.org/10.7326/M18-0759