Maria Salgado1, Mi Kwon2, Cristina Gálvez3, Jon Badiola4, Monique Nijhuis5, Alessandra Bandera6, Pascual Balsalobre2, Pilar Miralles2, Ismael Buño2, Carolina Martinez-Laperche2, Cristina Vilaplana7, Manuel Jurado4, Bonaventura Clotet8, Annemarie Wensing5, Javier Martinez-Picado9, Jose Luis Diez-Martin10. 1. IrsiCaixa AIDS Research Institute, Badalona, Spain (M.S.). 2. Gregorio Marañón G. University Hospital, Gregorio Marañón Health Research Institute, Madrid, Spain (M.K., P.B., P.M., I.B., C.M.). 3. IrsiCaixa AIDS Research Institute, Badalona, Spain, and Autonomous University of Barcelona, Barcelona, Spain (C.G.). 4. Virgen de las Nieves University Hospital, Granada, Spain (J.B., M.J.). 5. University Medical Center Utrecht, Utrecht, the Netherlands (M.N., A.W.). 6. San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy (A.B.). 7. Germans Trias i Pujol Research Institute, Badalona, Spain, Universitat Autònoma de Barcelona, Barcelona, Spain, and CIBER Enfermedades Respiratorias, Madrid, Spain (C.V.). 8. IrsiCaixa AIDS Research Institute, Badalona, Spain, and University of Vic - Central University of Catalonia, Vic, Spain (B.C.). 9. IrsiCaixa AIDS Research Institute, Badalona, Spain, University of Vic - Central University of Catalonia, Vic, Spain, and Catalan Institution for Research and Advanced Studies, Barcelona, Spain (J.M.). 10. Gregorio Marañón G. University Hospital, Gregorio Marañón Health Research Institute, and Complutense University of Madrid, Madrid, Spain (J.L.D.).
Abstract
This article has been corrected. The original version (PDF) is appended to this article as a Supplement. 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 wild-type 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-versus-host 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. Primary Funding Source: The Foundation for AIDS Research (amfAR).
This article has been corrected. The original version (PDF) is appended to this article as a Supplement. 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 wild-type 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-versus-host 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. Primary Funding Source: The Foundation for AIDS Research (amfAR).
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