Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals
Koelsch KK., Rasmussen TA., Hey-Nguyen WJ., Pearson C., Xu Y., Bailey M., Marks KH., Sasson SC., Taylor MS., Tantau R., Obeid S., Milner B., Morrissey O., Pinto AN., Suzuki K., Busch MP., Keating SM., Kaiser P., Yukl S., Wong JK., Hiener BM., Palmer S., Zaunders J., Post JJ., Chan DJ., Avery S., Milliken ST., Kelleher AD., Lewin SR., Cooper DA.
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. Methods: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4+ T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4+ T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. Results: All patients have been in continued remission for 4–6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir–related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. Conclusions: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.