HIV+ individuals are at increased risk of developing the malignancies that require allogeneic stem cell transplants (ASCT). While there is increasing evidence of the safety of ASCT in HIV+ individuals on antiretroviral therapy (ART), there has been little evaluation of the kinetics of immune reconstitution.
We prospectively evaluated HIV and CMV viral loads, and immune reconstitution measured by CD4 and CD8 peripheral T cell counts in six HIV+ individuals on ART undergoing ASCT for haematological malignancies. T cell subsets were compared with HIV-negative ASCT controls (n=17). Four HIV ASCT subjects also consented to fine-needle biopsy (FNB) of inguinal lymph-nodes pre and up to 4 years post-ASCT, and these findings were compared to non-ASCT HIV+ (treated n=11, untreated n=10) and HIV-negative (n=10) controls. Frozen PBMC were available for two subjects and we performed additional detailed flow cytometric characterisation to determine CD4 and CD8 subsets.
Characteristics for HIV-ASCT subjects can be found in Table 1. There were no significant differences in CD4 T cell counts between HIV ASCT subjects (median, IQR=367, 188 cells/µl) and controls (484, 444 cells/ µl) at time-points ~6-12 months post-ASCT. In contrast, CD8 T cells trended higher in HIV-ASCT subjects (1693, 1556 cells/ µl) vs controls (748, 922 cells/ µl; p=NS). In two subjects, both with elevated CD8 counts, further characterisation showed that one individual had elevated activated, non-gut homing, terminally differentiated CD8 T cells, while the other predominantly had activated, gut homing CD8 T cells. Comparisons of FNB T cells showed significantly lower CD4 T cells in HIV-ASCT (median, IQR = 3.1×104, 1.5×105 cells), compared to both HIV+ non-ASCT subjects, on ART (2.3×105, 1.9×105 cells) and untreated (5.9×105, 1.1×106 cells) and HIV-negative non-ASCT controls (8.9×105, 9.8 x105 cells).
HIV-ASCT individuals showed comparable peripheral blood recovery of CD4 T-cells, but increased numbers of CD8 T-cells post-ASCT – with detailed flow cytometry showing that the subsets that make up these elevated CD8 T cells appear to vary between subjects. The FNB data suggests that, compared with non-ASCT controls, nodal CD4 T cell recovery is impaired, even several years post-ASCT. While subject numbers are limited, the differences seen here suggest that co-infections and HIV associated factors, such as pre-existing immune impairment, may impact immune reconstitution.