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

Jingmei Hsu; Koen Van Besien; Marshall J Glesby; Savita Pahwa; Anne Coletti; Meredith G Warshaw; Larry Petz; Theodore B Moore; Ya Hui Chen; Suresh Pallikkuth; Adit Dhummakupt; Ruth Cortado; Amanda Golner; Frederic Bone; Maria Baldo; Marcie Riches; John W Mellors; Nicole H Tobin; Renee Browning; Deborah Persaud; Yvonne Bryson; International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1107 Team

doi:10.1016/j.cell.2023.02.030

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

Cell. 2023 Mar 16;186(6):1115-1126.e8. doi: 10.1016/j.cell.2023.02.030.

Authors

Jingmei Hsu¹, Koen Van Besien², Marshall J Glesby³, Savita Pahwa⁴, Anne Coletti⁵, Meredith G Warshaw⁶, Larry Petz⁷, Theodore B Moore⁸, Ya Hui Chen⁹, Suresh Pallikkuth¹⁰, Adit Dhummakupt⁹, Ruth Cortado¹¹, Amanda Golner¹², Frederic Bone¹², Maria Baldo², Marcie Riches¹³, John W Mellors¹⁴, Nicole H Tobin¹¹, Renee Browning¹⁵, Deborah Persaud⁹, Yvonne Bryson¹¹; International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1107 Team¹⁶

Collaborators

International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1107 Team:
Patricia Anthony, Frederic Bone, Renee Browning, Yvonne Bryson, Anne Coletti, Marshall J Glesby, Amanda Golner, Rohan Hazra, Jingmei Hsu, Ronald Mitsuyasu, Theodore B Moore, Savita Pahwe, Deborah Persaud, Lawrence Petz, Nicole H Tobin, Meredith G Warshaw, Dwight Yin

Affiliations

¹ Department of Medicine, Division of Hematology & Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY 10021, USA. Electronic address: jingmei.hsu@nyulangone.org.
² Department of Medicine, Division of Hematology & Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY 10021, USA.
³ Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY 10021, USA.
⁴ Department of Microbiology and Immunology, Pediatrics and Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
⁵ Family Health International 360, Durham, NC 27761, USA.
⁶ Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, MA 02115, USA.
⁷ StemCyte International Cord Blood Center, Baldwin Park, CA 91706, USA.
⁸ Department of Pediatrics, Division of Hematology& Oncology, Ronald Reagan UCLA Medical Center, Los Angeles, CA 90095, USA.
⁹ Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA.
¹⁰ Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
¹¹ Department of Pediatrics, Division of Infectious Diseases, Mattel Children's, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹² Frontier Science & Technology Research Foundation, Inc, Amherst, NY 14226, USA.
¹³ Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin Clinical Cancer Center, Milwaukee, WI 53226, USA.
¹⁴ Department of Medicine, Division of Infectious Diseases, University of Pittsburg School of Medicine, Pittsburgh, PA 15261, USA.
¹⁵ National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
¹⁶ IMPAACT Operations Center, FHI 360, 359 Blackwell St, Ste 200, Durham, NC 27701, USA.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02140944.

Keywords: HIV CCR5 dela 32 transplant; HIV cure; HIV remission.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Cord Blood Stem Cell Transplantation*
Female
Fetal Blood
HIV Infections*
HIV-1*
Hematopoietic Stem Cell Transplantation*
Humans
Leukemia, Myeloid, Acute* / therapy
Male

Associated data

ClinicalTrials.gov/NCT02140944

Abstract

Publication types

MeSH terms

Associated data

Grants and funding