Altered Immune Reconstitution in Allogeneic Stem Cell Transplant Recipients With Human Immunodeficiency Virus (HIV)

Abstract

Background: Persons living with human immunodeficiency virus (HIV) are at elevated risk of developing the malignant diseases that require allogeneic stem cell transplantation (ASCT). Recent data suggest that these individuals are also at an elevated risk of certain complications post-ASCT. This risk may result from preexisting HIV-related factors affecting dynamics of immune reconstitution post-ASCT. However, to date, there has been little work describing the dynamics of immune reconstitution post-ASCT in persons with HIV and none comparing these data to controls without HIV.

Methods: We assessed T-cell reconstitution in 6 ASCT with HIV recipients (HIV+ASCT) compared to a control population of 21 ASCT without HIV recipients. In a subset of HIV+ASCT recipients we performed additional flow cytometry profiling of CD8+ T-cell subsets and antigen specificity of reconstituting CD4+ and CD8+ T cells.

Results: We observe no difference in post-ASCT CD4+ T cells between HIV+ASCT and HIV-negative ASCT recipients, despite much lower pre-ASCT CD4+ T-cell counts in the HIV+ASCT group. In contrast, we observed significantly higher CD8+ T-cell numbers in the HIV+ASCT group post-ASCT. The reconstituting CD8+ T-cells were predominantly CD45RO+, whereas homing markers and antigen specificity of these cells varied between participants.

Conclusion: This study represents the most extensive characterization of immune-reconstitution post-ASCT in persons with HIV, and the first to our knowledge to compare these data to ASCT controls without HIV. The results indicate that immune reconstitution in this group can be affected by preexisting HIV infection and post-ASCT antigen exposure.

Keywords: HIV; acute leukemia; allogeneic stem cell transplant; immune reconstitution; lymphoma.

Figure 1.

A, CD4+ T cells and CD8+ T cells, measured between 7 and 12 months post-ASCT, of HIV+ASCT and ASCT controls. There were no differences between the CD4+ T-cell counts of HIV+ASCT (median = 367 cells/µL [IQR = 283–471]) and ASCT controls (313 cells/µL [176–620]). However, CD8+ T cells were significantly higher in HIV+ASCT subjects (1676 cells/µL [670–2226]) compared to ASCT controls (550 cells/µL [328–1280]). B, Longitudinal CD8+ T-cell counts for available measurements in HIV+ASCT participants. Abbreviations: ASCT, allogeneic stem cell transplantation; HIV, human immunodeficiency virus; IQR, interquartile range.

Figure 2.

A, Flow cytometric characterization of CD8+ T-cell subsets post-ASCT in 3 HIV+ASCT individuals. Pt-1 predominantly had an elevation of CD45RO+ non-gut homing CD8+ T-cells post-ASCT. Pt-2 had an elevation of CD45RO+ activated (CD38+) gut-homing CD8+ T cells, particularly at 7–8 months post-transplant. No clear expansion of CD45RO+ CD8+ T cells was observed in Pt-5; therefore, CD38+ data are not presented for this patient. Subsets are presented as percentages of total CD8+ T cells. B, Flow cytometric data on CD8+ T cells compared to a group of HCs. The ASCT with HIV group exhibited a much higher percentage of memory CD45RO+ CD8+ T cells and highly activated CD38+CD127- CD8+ T cells than HCs. The data from the ASCT with HIV group came from time-points 7, 8, and 9 months post-ASCT for Pt-1, 2, and 5, respectively. Abbreviations: ASCT, allogeneic stem cell transplantation; HC, healthy control; HIV, human immunodeficiency virus; Pt, patient.