title: Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation.
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.
authors: Divison of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Timothy J
authors: TJ
authors: Henrich
authors: Zixin
authors: Z
authors: Hu
authors: Jonathan Z
authors: JZ
authors: Li
authors: Gaia
authors: G
authors: Sciaranghella
authors: Michael P
authors: MP
authors: Busch
authors: Sheila M
authors: SM
authors: Keating
authors: Sebastien
authors: S
authors: Gallien
authors: Nina H
authors: NH
authors: Lin
authors: Francoise F
authors: FF
authors: Giguel
authors: Laura
authors: L
authors: Lavoie
authors: Vincent T
authors: VT
authors: Ho
authors: Philippe
authors: P
authors: Armand
authors: Robert J
authors: RJ
authors: Soiffer
authors: Manish
authors: M
authors: Sagar
authors: Ann S
authors: AS
authors: Lacasce
authors: Daniel R
authors: DR
authors: Kuritzkes
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D017353:Gene Deletion; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification* / Q000472:pathogenicity; D006579:Heterozygote; D006801:Humans; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D019713:Receptors, CCR5; D015728:Receptors, HIV