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Background: To date, the only and most compiling evidence of a medical intervention that has been able to cure HIV-1 infection (the “Berlin patient”), involved an allogeneic stem cell transplant (SCT) from a donor who was homozygous for CCR5Δ32. Although this high-risk procedure is only indicated for certain hematological malignancies, the strategy raised tremendous scientific potential to gain insight in the mechanisms of HIV eradication.
Methods: The EpiStem 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 included in the EPISTEM observational cohort. Detailed analysis of the cohort should provide insight as to whether additional factors such as conditioning regimen, total body irradiation and graft versus host disease may contribute to the eradication of the potentially infectious viral reservoir in addition to the lack of a functional CCR5 receptor.
Results: Nearly 30,000 cord blood units in multiple European blood banks and more than 1.000.000 adult donors have been genotyped for CCR5 to generate a registry of CCR5Δ32 available donors. Twenty HIV positive patients with diverse hematological malignancies have been registered to the EPISTEM cohort. Since 2012, 13 patients have been transplanted; 4 with a CCR5Δ32, 1 with a heterozygous, and 8 with a CCR5 WT donor. In 3 cases the donor cells came from cord blood and in 10 cases from an adult donor. So far, 5 patients have successfully passed the 12 months follow-up after transplantation, and 8 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 to very low levels.
Conclusions: EPISTEM is actively recruiting new cases and continues to systematically investigate HIV persistence over time to gain insight in potential HIV-1 eradication.