Mechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant

Mechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant

Online publication: 15/10/2018 Journal: Annals of Internal Medicine

Abstract:

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).

Authors: Maria Salgado, PhD; Mi Kwon, MD; Cristina Gálvez, MS; Jon Badiola, MD; Monique Nijhuis, PhD; Alessandra Bandera, MD, PhD; Pascual Balsalobre, PhD; Pilar Miralles, MD; Ismael Buño, PhD; Carolina Martinez-Laperche, PhD; Cristina Vilaplana, MD, PhD; Manuel Jurado, MD, PhD; Bonaventura Clotet, MD, PhD; Annemarie Wensing, MD; Javier Martinez-Picado, PhD; Jose Luis Diez-Martin, MD, PhD; for the IciStem Consortium.

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