Abstract Body

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only medical intervention which has led to HIV cure. While the size of 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 HIV-infected patients who underwent allo-HSCT (including 4 individuals who received cells from CCR5D32/D32 donors) to treat their underlying hematological malignancy and remained under antiretroviral therapy (ART).

We found that reconstitution of the CD4+ and CD8+ T-cell compartment was slow and heterogeneous with an initial expansion of activated CD4+ T-cells that preceded the expansion of CD8+ T-cells. Transplanted patients did not achieve full immune reconstitution after allo-HSCT. While HIV-specific CD8+ T-cells disappeared immediately after allo-HSCT, weak ex vivo HIV-specific CD8+ T-cell responses were detectable several weeks after allo-HSCT, 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 to 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.