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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3484-3487. Prepublished online as a Blood First Edition Paper on August 12, 2008; DOI 10.1182/blood-2008-05-157511.
Submitted May 15, 2008
Fred Hutchinson Cancer Research Center, Seattle, WA, United States * Corresponding author; email: awoolfre{at}fhcrc.org.
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 anti-retroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and post-transplant cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1-specific CD8+ cell immune responses were compared before and after HCT. Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and following HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8+ T-cell responses targeting multiple epitopes were detected prior to HCT. Following 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.
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