Cord Blood Transplantation for Cure of HIV Infections

Abstract

HIV infection has not been cured by antiretroviral drugs or gene therapy, but it has been cured by a hematopoietic cell transplantation (HCT) that was performed for a patient with acute myeloid leukemia and HIV infection using peripheral blood stem cells from an adult donor homozygous for CCR5-Δ32 (CCR5-Δ32/Δ32). HIV has remained undetectable more than 6 years after discontinuation of antiretroviral therapy. However, this approach cannot be readily generalized because of the low prevalence of the CCR5-Δ32 allele and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients, as when bone marrow or peripheral blood stem cell transplants are performed. In contrast, cord blood (CB) transplants require less stringent HLA matching. CB units are being screened to develop an inventory of cryopreserved homozygous CCR5-Δ32 units available for HCT. One hundred eighty homozygous CCR5-Δ32 units have been identified, and 300 units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA-matched unit with a minimal cell dose of ≥2.5 × 10(7) total nucleated cells (TNC) per kilogram and for white adults a 27.9% probability. With a minimal cell dose requirement of ≥1 × 10(7) TNC per kilogram, the corresponding projected probabilities are 85.6% and 82.1%. CB transplantation does not require as stringent an HLA match between donor and recipient as bone marrow or peripheral blood HCTs, and HCT using cord bloods from donors homozygous for CCR5-Δ32 is, at the present time, the only feasible means of treatment of reasonable numbers of patients who are infected with HIV.