Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation

TJ Henrich, Z Hu, JZ Li, G Sciaranghella… - The Journal of …, 2013 - academic.oup.com
TJ Henrich, Z Hu, JZ Li, G Sciaranghella, MP Busch, SM Keating, S Gallien, NH Lin…
The Journal of infectious diseases, 2013academic.oup.com
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 …
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.
Oxford University Press