Background: HIV-1 cure has been reported in two men with HIV-1 and malignancy following CCR5?32 homozygousallogeneic adult stem cell transplantation. We report on a woman in ART-free HIV-1 remission for 14months following CCR5?32 homozygous cord blood (CB) and CD34-selected haploidentical stem celltransplant (haplo-cord SCT) for acute myeloid leukemia (AML).
Methods: IMPAACT P1107 is an observational study of HIV-1 persistence pre- and post- CCR5?32/?32 CBtransplantation for other diseases. Transplant data are from the Center for International Blood andMarrow Transplant Research. Pre- and post-transplant levels of HIV-1 DNA, 2-LTR-circles, and size ofthe latent replication-competent reservoir (IUPM), plasma viremia (single copy level), HIV-1 antibody,cellular immune phenotypic responses, and HIV-1 tropism were assessed.
Results: This middle-aged U.S. woman of mixed race developed high-risk AML while on ART, 4 years afterdiagnosis of acute HIV-1. She underwent reduced intensity CCR5?32/?32 haplo-cord SCT andachieved AML remission with a 100% CCR5?32/?32 CB chimerism by day 100 post-transplant andthereafter. She had early hospital discharge, no acute or chronic GVHD, and asymptomatic CMV andEBV reactivation. Figure 1 shows HIV-1 viral load, antiretroviral treatment, and immune reconstitutionprofiles. At 37 months post-transplant, she stopped ART (ATI) and has remained aviremic < 1cp/mlfor 14 months. Pre-transplant: HIV-1 DNA (137.4 Gag c/106 PBMC); 2-LTR circles (6.3 c/106 PBMC); plasma HIVRNA (3.3 c/mL); latent reservoir (LR=1.38 IUPM) were all detectable. The proviral pool was CCR5tropic; she was HIV-1 antibody indeterminate. Post-transplant: HIV-1 DNA became undetectable (<4.06 c/106 cells), including in CD4+ T cells andbone marrow. Trace levels of 2-LTR circles were transiently detected only at 12 weeks post ATI. LRsize was <0.009 IUPM. She is HIV-1 seronegative and has no HIV-1 specific T cell response to Gag.Her engrafted cells show ex-vivo resistance to infection by autologous LR isolates and CCR5/X4 tropiclab strains. No ARVs were detected at multiple timepoints post-ATI.
Conclusions: This is the third known case of HIV-1 remission, the first known case in a woman of mixed race, andthe first known case with haplo-cord CCR5?32/?32 SCT. Broader use of CCR5?32/?32 haplo-cordtransplantation should be considered to achieve HIV-1 remission and cure for persons living with HIV-1 requiring SCT for other diseases.