HIV-1 remission and possible cure in a woman after haplo-cord blood transplant

• Published in: Cell 2023-03, Vol.186 (6), p.1115-1126.e8
• Main Authors: Hsu, Jingmei, Van Besien, Koen, Glesby, Marshall J., Pahwa, Savita, Coletti, Anne, Warshaw, Meredith G., Petz, Lawrence D., Moore, Theodore B., Chen, Ya Hui, Pallikkuth, Suresh, Dhummakupt, Adit, Cortado, Ruth, Golner, Amanda, Bone, Frederic, Baldo, Maria, Riches, Marcie, Mellors, John W., Tobin, Nicole H., Browning, Renee, Persaud, Deborah, Bryson, Yvonne, Anthony, Patricia, Hazra, Rohan, Mitsuyasu, Ronald, Pahwe, Savita, Petz, Lawrence, Yin, Dwight
• Format: Article
• Language: English
• Subjects: Adult; adult stem cells; adults; ancestry; antiretroviral agents; blood; chimerism; Cord Blood Stem Cell Transplantation; Female; Fetal Blood; Hematopoietic Stem Cell Transplantation; HIV CCR5 dela 32 transplant; HIV cure; HIV Infections; HIV remission; HIV-1; homozygosity; Humans; Leukemia, Myeloid, Acute - therapy; Male; myeloid leukemia; remission; therapeutics; women
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2023.02.030

Previously, two men were cured of HIV-1 through CCR5Δ32 homozygous (CCR5Δ32/Δ32) allogeneic adult stem cell transplant. We report the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML). Peripheral blood chimerism was 100% CCR5Δ32/Δ32 cord blood by week 14 post-transplant and persisted through 4.8 years of follow-up. Immune reconstitution was associated with (1) loss of detectable replication-competent HIV-1 reservoirs, (2) loss of HIV-1-specific immune responses, (3) in vitro resistance to X4 and R5 laboratory variants, including pre-transplant autologous latent reservoir isolates, and (4) 18 months of HIV-1 control with aviremia, off antiretroviral therapy, starting at 37 months post-transplant. CCR5Δ32/Δ32 haplo-cord transplant achieved remission and a possible HIV-1 cure for a person of diverse ancestry, living with HIV-1, who required a stem cell transplant for acute leukemia. [Display omitted] •First mixed-race woman with HIV-1 remission post CCR5Δ32/Δ32 haplo-cord transplant•100% immune reconstitution by CCR5Δ32/Δ32 cord graft and resistance to HIV strains•No HIV viral rebound ≥18 months off antiretroviral therapy without graft vs. host disease•No detectable HIV-1 DNA/RNA, replication competent virus & loss of HIV Ab response Following the previous cure of two men of HIV-1 through allogenic stem cell transplantation procedures, a study reports a broader application of this approach by demonstrating the first such possible cure in a mixed-race woman using CCR5Δ32/Δ32 haplo-cord transplant to treat acute myeloid leukemia. This transplant resulted in resistance to HIV strains, and no detectable virus was seen even with the removal of antiretroviral medications.