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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.


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Submitted May 15, 2008
Accepted July 25, 2008

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

Ann E. Woolfrey*, Uma Malhotra, Robert D Harrington, John McNevin, Thomas J Manley, Stanley R. Riddell, Robert W. Coombs, Frederick R. Appelbaum, Larry Corey, and Rainer Storb

Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Infectious Diseases, Virginia Mason Medical Center, Seattle, WA, United States
Infectious Disease, University of Washington, 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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