Long-Term Reduction in Peripheral Blood HIV Type 1 Reservoirs Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation
Timothy J. Henrich,Timothy J. Henrich,Zixin Hu,Zixin Hu,Jonathan Z. Li,Jonathan Z. Li,Gaia Sciaranghella,Michael P. Busch,Michael P. Busch,Sheila M. Keating,Sheila M. Keating,Sébastien Gallien,Nina H. Lin,Francoise Giguel,Laura Lavoie,Vincent T. Ho,Philippe Armand,Robert J. Soiffer,Manish Sagar,Manish Sagar,Ann S. LaCasce,Daniel R. Kuritzkes,Daniel R. Kuritzkes +22 more
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TLDR
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 patients receiving combination antiretroviral therapy (cART).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 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.read more
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References
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Sarah Palmer,Frank Maldarelli,Ann Wiegand,Barry Bernstein,George J. Hanna,Scott C. Brun,Dale J. Kempf,John W. Mellors,John M. Coffin,Martin S. King +9 more
TL;DR: Analysis of longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial suggests that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second inWhich viral production remains stable for at least 7 years.
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