%0 Journal Article
%A Eberhard, Johanna M
%A Angin, Mathieu
%A Passaes, Caroline
%A Salgado, Maria
%A Monceaux, Valerie
%A Knops, Elena
%A Kobbe, Guido
%A Jensen, Björn
%A Christopeit, Maximilian
%A Kröger, Nicolaus
%A Vandekerckhove, Linos
%A Badiola, Jon
%A Bandera, Alessandra
%A Raj, Kavita
%A van Lunzen, Jan
%A Hütter, Gero
%A Kuball, Jürgen H E
%A Martinez-Laperche, Carolina
%A Balsalobre, Pascual
%A Kwon, Mi
%A Díez-Martín, José L
%A Nijhuis, Monique
%A Wensing, Annemarie
%A Martinez-Picado, Javier
%A Schulze Zur Wiesch, Julian
%A Sáez-Cirión, Asier
%T Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1.
%D 2020
%U http://hdl.handle.net/10668/15523
%X 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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