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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).

SUBMITTER: Woolfrey AE 

PROVIDER: S-EPMC2569185 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Generation of HIV-1-specific CD8+ cell responses following allogeneic hematopoietic cell transplantation.

Woolfrey Ann E AE   Malhotra Uma U   Harrington Robert D RD   McNevin John J   Manley Thomas J TJ   Riddell Stanley R SR   Coombs Robert W RW   Appelbaum Frederick R FR   Corey Larry L   Storb Rainer R  

Blood 20080812 8


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 compa  ...[more]

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