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Introduction We report the results of a phenotypic and functional analysis of immune reconstitution in HIV(+) patients treated with allogeneic hematopoietic stem cell transplant (allo-HSCT), in comparison with HIV(+) autologous transplant (auto-HSCT) recipients, HIV(-) auto-HSCT recipients and healthy controls (HCs). Methods Blood samples were collected at days 56, 180 and 365 post-transplant from HIV(+) allo-ASCT recipients (n=17, BMT-CTN-0903/AMC-080 trial), HIV(+) auto-SCT recipients (n=36, BMT-CTN-0803/AMC-071 trial) and HIV(-) auto-SCT recipients (n=30, NCT00569309/OSU-07044 trial), and at 1 time point from 71 HCs. Five-color flow cytometry was performed on whole blood. Principal component analysis (PCA) examined global differences across 18 immune cell subsets between all subject cohorts. Wilcoxon rank-sum tests compared median absolute and proportionate cell counts. Feature importance score analysis (FIS) identified contributions of 100 immune cell populations to differences between HIV(+) cohorts and HCs. Functional responsiveness of HIV(+) allo-HSCT recipients' T cells to stimulation with CD3- and CD28-directed antibodies, NK cells to stimulation with IL-12+IL-18 and monocytes to stimulation with lipopolysaccharide (LPS) was assessed by mass cytometry on peripheral blood mononuclear cells (n=2) and compared to HCs (n=2). Results PCA showed that immunomes of HIV(+) allo-HSCT recipients and HIV(+) auto-HSCT recipients clustered together at all time points. HIV(-) auto-SCT recipients and HCs clustered together and away from the HIV(+) cohorts. FIS identified 13 cell subsets that defined the difference between HIV(+) allo-HSCT recipients (all visits) and HCs and 11 immune cell subsets that defined the difference between HIV(+) auto-HSCT recipients (all visits) and HCs; in each comparison, activated CD3+/HLA-DR+ T cells had the greatest impact on the difference between composite HIV(+) and HC immunomes. At 1 year, both HIV(+) transplant recipient cohorts had higher absolute numbers of activated T cells, effector T cells and CD8+ T cells than HCs and lower numbers of CD4+ T cells, naive T cells, and activated NK cells compared to HCs (p Conclusion Chronic HIV infection confers pro-inflammatory immune characteristics on phenotypic and functional profiling of the cellular immunome of stem cell transplant recipients, irrespective of allogeneic or autologous stem cell donor source.

Intensive chemotherapy for human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) has resulted in durable remissions in a substantial proportion of patients. High-dose chemotherapy and autologous stem cell transplantation (AuSCT), moreover, has resulted in sustained complete remissions in selected patients with recurrent chemosensitive disease. Based on a favorable experience with dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT for older patients with non-HIV–associated aggressive lymphomas, an AIDS Malignancy Consortium multicenter trial was undertaken using the same dose-reduced busulfan and cyclophosphamide preparative regimen with AuSCT for recurrent HIV-associated NHL and HL. Of the 27 patients in the study, 20 received an AuSCT. The median time to achievement of an absolute neutrophil count (ANC) of ≥ 0.5×10 9 /L was 11 days (range, 9-16 days). The median time to achievement of an unsupported platelet count of ≥ 20×10 9 /L was 13 days (range, 6-57 days). One patient died on day +33 posttransplantation from hepatic veno-occlusive disease (VOD) and multiorgan failure. No other fatal regimen-related toxicity occurred. Ten of 19 patients (53%) were in complete remission at the time of their day +100 post-AuSCT evaluation. Of the 20 patients, 10 were alive and event-free at a median of 23 weeks post-AuSCT. Median overall survival (OS) was not reached by 13 of the 20 patients alive at the time of last follow-up. This multi-institutional trial demonstrates that a regimen of dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT is well tolerated and is associated with favorable disease-free survival (DFS) and OS probabilities for selected patients with HIV-associated NHL and HL.