Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterisation of HIV infected patients undergoing HSCT is warranted. Methods: We studied three 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 (PBMCs), isolated CD4+ T cells from peripheral blood and lymph node cells. The patients remained on ART 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 three patients, changes in immune response varied with pronounced reductions in two patients and a less dramatic reduction in one patient. One patient experienced unexpected viral rebound 4 years after HSCT. Conclusion: These three cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in one patient indicates that replication competent HIV can re-emerge several years following HSCT despite these marked changes.

Allogeneic Hematopoietic Cell Transplant for HIV Patients with Hematologic Malignancies: The BMT CTN-0903/AMC-080 Trial

“…However, in patients who received CCR5 wild-type donors in this series and achieved complete donor chimerism, HIV-1 was not detected in PBMCs using a sensitive quantitative PCR assay for proviral DNA [17] and infectious virus was not detected using a quantitative viral outgrowth assay. This is consistent with earlier reports that when complete T cell donor chimerism is achieved, the number of HIV-infected cells in blood is reduced to levels below the limits of detection of these assays [10,26,27]. These reductions in HIV-infected blood cells in peripheral blood do not mean that all infected cells including those with intact (replication-competent) proviruses were eliminated.…”

No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication

“…Reports of successful HIV cure after bone marrow transplant and reports of long-term suppression of HIV following discontinuation of cART in some individuals show that both eradication and functional control of HIV are possible (1)(2)(3)(4)(5). The fact that these are rare events that were not observed in others undergoing bone marrow transplant (6)(7)(8) means that improving the outcomes for the majority of treated individuals will require a better understanding of the sources and mechanisms of HIV persistence during therapy. Two distinct mechanisms have been proposed to explain how the population of cells containing replication-competent HIV, denoted the HIV reservoir, are maintained in individuals undergoing successful cART: long-term persistence and clonal expansion of HIV-infected cells, and, alternatively, ongoing cycles of active HIV infection that continuously replenish the HIV reservoir.…”

How I treat patients with HIV-related hematological malignancies using hematopoietic cell transplantation

“…67 Even in the absence of a detectable viral load, donor-derived anti-HIV T-cell responses can be generated, as was confirmed by a recent report about 3 additional alloHCT patients. 68 These data suggest the possibility of a graftversus-HIV effect.…”