Background: Allogeneic Stem Cell Transplantation (SCT) in HIV infected individuals has the potential to cure HIV as has been observed in the Berlin patient. Although this high-risk procedure is only indicated for certain hematological malignancies, the strategy raised tremendous scientific potential to gain profound insight in the mechanisms of HIV eradication.
Methods: The IciStem consortium aims to guide clinicians of HIV-infected patients who require an SCT in donor search and CCR5 screening, ethical regulations, the SCT procedure, sampling procedures and in depth investigations to study HIV persistence. The patients are registered to the IciStem observational cohort. Viral tropism, the remaining HIV reservoir and cellular and humoral immunity are investigated thoroughly.
Results: As part of IciStem efforts, 32,000 cord blood units and 2,200,000 bone marrow adult donors have been genotyped for CCR5 in multiple blood banks around Europe to increase CCR5Δ32 donor availability. 44 HIV-positive patients with diverse hematological malignancies have been registered to the IciStem cohort. 38 patients have been transplanted with CCR5Δ32 (n=9), heterozygous (n=3) or CCR5 WT donors. So far, 19 patients have successfully passed the 12 months follow-up after transplantation, and 13 patients have died after transplantation, despite achieving full donor chimerism in most cases. Preliminary analysis of virological and immunological data from blood and tissue samples shows a systematic reduction of HIV-1 reservoirs and a diminishing humoral immunity with (partial) seroreversion. Out of the 4 patients with a CCR5Δ32 homozygous donor that are still on follow up, two patients have interrupted antiviral therapy and did not rebound during the observation time. Five CCR5WT participants with proven undetectable viral reservoirs are in the process of initiating a combination of an immune therapy (bNAbs: 10-1074+3BNC117) with ATI.
Conclusions: IciStem is the largest registry studying in depth the HIV reservoir and the respective immune system after allo-HSCT. A potential eradication of the reservoir is currently evaluated by treatment interruption alone or in combination with bNAbs.