title: Generation of HIV-1-specific CD8+ cell responses following allogeneic hematopoietic cell transplantation.
abstract: This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1-specific CD8(+) cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8(+) T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1-specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA. awoolfre@fhcrc.org
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.forename: Uma
authors.initials: U
authors.lastname: Malhotra
authors.forename: Robert D
authors.initials: RD
authors.lastname: Harrington
authors.forename: John
authors.initials: J
authors.lastname: McNevin
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Manley
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Larry
authors.initials: L
authors.lastname: Corey
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D016572:Cyclosporine / Q000008:administration & dosage; D000939:Epitopes / Q000737:chemistry; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D015497:HIV-1 / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D014184:Transplantation, Homologous
chemical_list: D000939:Epitopes; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid