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Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1

Johanna M Eberhard 1, 2 Mathieu Angin 3 Caroline Passaes 3 Maria Salgado 4 Valerie Monceaux 3 Elena Knops 5 Guido Kobbe 6 Björn Jensen 6 Maximilian Christopeit 7 Nicolaus Kröger 7 Linos Vandekerckhove 8 Jon Badiola 9 Alessandra Bandera 10 Kavita Raj 11 Jan van Lunzen 1, 12 Gero Hütter 13 Jürgen H E Kuball 14 Carolina Martinez-Laperche 15, 16 Pascual Balsalobre 15, 16 Mi Kwon 15, 16 José L Díez-Martín 15, 16 Monique Nijhuis 14 Annemarie M Wensing 14 Javier Martinez-Picado 4, 17, 18 Julian Schulze Zur Wiesch 1, 2, * Asier Sáez-Cirión 3, * 
Abstract : Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only medical intervention that has led to an HIV cure. Whereas the HIV reservoir sharply decreases after allo-HSCT, the dynamics of the T cell reconstitution has not been comprehensively described. We analyzed the activation and differentiation of CD4+ and CD8+ T cells, and the breadth and quality of HIV- and CMV-specific CD8+ T cell responses in 16 patients with HIV who underwent allo-HSCT (including five individuals who received cells from CCR5Δ32/Δ32 donors) to treat their underlying hematological malignancy and who remained on antiretroviral therapy (ART). We found that reconstitution of the T cell compartment after allo-HSCT was slow and heterogeneous with an initial expansion of activated CD4+ T cells that preceded the expansion of CD8+ T cells. Although HIV-specific CD8+ T cells disappeared immediately after allo-HSCT, weak HIV-specific CD8+ T cell responses were detectable several weeks after transplant and could still be detected at the time of full T cell chimerism, indicating that de novo priming, and hence antigen exposure, occurred during the time of T cell expansion. These HIV-specific T cells had limited functionality compared with CMV-specific CD8+ T cells and persisted years after allo-HSCT. In conclusion, immune reconstitution was slow, heterogeneous, and incomplete and coincided with de novo detection of weak HIV-specific T cell responses. The initial short phase of high T cell activation, in which HIV antigens were present, may constitute a window of vulnerability for the reseeding of viral reservoirs, emphasizing the importance of maintaining ART directly after allo-HSCT.
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Johanna M Eberhard, Mathieu Angin, Caroline Passaes, Maria Salgado, Valerie Monceaux, et al.. Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1. Science Translational Medicine, American Association for the Advancement of Science (AAAS), 2020, 12 (542), pp.eaay9355. ⟨10.1126/scitranslmed.aay9355⟩. ⟨pasteur-02870497⟩



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