Background.The long-term impact of allogeneic hematopoietic stem cell transplantation (HSCT) on human immunodeficiency virus type 1 (HIV-1) reservoirs in patients receiving combination antiretroviral therapy (cART) is largely unknown.Methods.We studied the effects of a reduced-intensity conditioning allogeneic HSCT from donors with wildtype-CCR5 + cells on HIV-1 peripheral blood reservoirs in 2 patients heterozygous for the ccr5Δ32 mutation.Indepth analyses of the HIV-1 reservoir size in peripheral blood, coreceptor use, and specific antibody responses were performed on samples obtained before and up to 3.5 years after HSCT receipt.Results.Although HIV-1 DNA was readily detected in peripheral blood mononuclear cells (PBMCs) before and 2-3 months after HSCT receipt, HIV-1 DNA and RNA were undetectable in PBMCs, CD4 + T cells, or plasma up to 21 and 42 months after HSCT.The loss of detectable HIV-1 correlated temporally with full donor chimerism, development of graft-versus-host disease, and decreases in HIV-specific antibody levels.Conclusions.The ability of donor cells to engraft without evidence of ongoing HIV-1 infection suggests that HIV-1 replication may be fully suppressed during cART and does not contribute to maintenance of viral reservoirs in peripheral blood in our patients.HSCTs with wild-type-CCR5 + donor cells can lead to a sustained reduction in the size of the peripheral reservoir of HIV-1.

Long-Term Reduction in Peripheral Blood HIV Type 1 Reservoirs Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation