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Timothy J. Henrich, Zixin Hu, Jonathan Z. Li, Gaia Sciaranghella, Michael P. Busch, Sheila M. Keating, Sebastien Gallien, Nina H. Lin, Francoise F. Giguel, Laura Lavoie, Vincent T. Ho, Philippe Armand, Robert J. Soiffer, Manish Sagar, Ann S. LaCasce, Daniel R. Kuritzkes, Long-Term Reduction in Peripheral Blood HIV Type 1 Reservoirs Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation, The Journal of Infectious Diseases, Volume 207, Issue 11, 1 June 2013, Pages 1694–1702, https://doi.org/10.1093/infdis/jit086
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Abstract
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 wild-type–CCR5+ cells on HIV-1 peripheral blood reservoirs in 2 patients heterozygous for the ccr5Δ32 mutation. In-depth 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.
