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

Publication Type:

Journal Article

Source:

Blood, Volume 112, Issue 8, p.3484-7 (2008)

Keywords:

2008, Adult, Antibody Development Core Facility, Antiretroviral Therapy, Highly Active, CD8-Positive T-Lymphocytes, Cell Processing Core Facility, Center-Authored Paper, Clinical Research Division, Cyclosporine, Cytokine Analysis Core Facility, Epitopes, Flow Cytometry Core Facility, hematopoietic stem cell transplantation, HIV Infections, HIV-1, Humans, Immune Monitoring Core Facility, Immune System, Immunosuppressive Agents, Leukemia, Myeloid, Acute, Male, Mycophenolic Acid, Research Trials Office Core Facility - Biostatistics Service, Scientific Imaging Core Facility, Shared Resources, Specialized Pathology Core Facility, Specimen Processing Core Facility, Transplantation, Homologous, Vaccine and Infectious Disease Institute

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).