Progress toward curing HIV infection with hematopoietic cell transplantation

Abstract

Lawrence D Petz,1 John C Burnett,2 Haitang Li,3 Shirley Li,3 Richard Tonai,1 Milena Bakalinskaya,4 Elizabeth J Shpall,5 Sue Armitage,6 Joanne Kurtzberg,7 Donna M Regan,8 Pamela Clark,9 Sergio Querol,10 Jonathan A Gutman,11 Stephen R Spellman,12 Loren Gragert,13 John J Rossi2 1StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 2Department of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, 3Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA; 4CCR5-Δ32/Δ32 Research Department, StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 5Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6MD Anderson Cord Blood Bank, Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Carolinas Cord Blood Bank, Duke University Medical Center, Durham, NC, USA; 8St Louis Cord Blood Bank, SSM Cardinal Glennon Children's Medical Center, St Louis, MO, USA; 9Enhance Quality Consulting Inc., Oviedo, FL, USA; 10Cell Therapy Service and Cord Blood Bank, Banc de Sang i Teixits, Barcelona, Spain; 11BMT/Hematologic Malignancies, University of Colorado, Aurora, CO, USA; 12Immunobiology and Observational Research, CIBMTR, Minneapolis, MN, USA; 13National Marrow Donor Program/Be The Match, Minneapolis, MN, USA Abstract: HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT) from a graft that carried the HIV-resistant CCR5-Δ32/Δ32 mutation. Other attempts to establish a cure for HIV/AIDS using HCT in patients with HIV-1 and malignancy have yielded mixed results, as encouraging evidence for virus eradication in a few cases has been offset by poor clinical outcomes due to the underlying cancer or other complications. Such clinical strategies have relied on HIV-resistant hematopoietic stem and progenitor cells that harbor the natural CCR5-Δ32/Δ32 mutation or that have been genetically modified for HIV-resistance. Nevertheless, HCT with HIV-resistant cord blood remains a promising option, particularly with inventories of CCR5-Δ32/Δ32 units or with genetically modified, human leukocyte antigen-matched cord blood. Keywords: curing HIV infection, hematopoietic cell transplantation, genetic modification of stem cells, CCR5 mutation, CCR5-Δ32/Δ32 cord blood inventory