Transplantation of CCR5∆32 homozygous umbilical cord blood in a child with acute lymphoblastic leukemia and perinatally acquired HIV infection

Meghan K Rothenberger, John E. Wagner, Ashley Haase, Douglas Richman, Bartosz J Grzywacz, Matthew Strain, Steven Lada, Jacob Estes, Courtney V. Fletcher, Anthony T. Podany, Jodi Anderson, Thomas Schmidt, Stephen W Wietgrefe, Timothy W Schacker, Michael R. Verneris

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9 Scopus citations

Abstract

Background. Allogeneic hematopoietic cell transplantation (allo-HCT) in a CCR5∆32 homozygous donor resulted in HIV cure. Understanding how allo-HCT impacts the HIV reservoir will inform cure strategies. Methods. A 12-year-old with perinatally acquired, CCR5-tropic HIV and acute lymphoblastic leukemia underwent myeloablative conditioning and umbilical cord blood (UCB) transplantation from a CCR5∆32 homozygous donor. Peripheral blood mononuclear cells (PBMCs) and the rectum were sampled pre- and post-transplant. The brain, lung, lymph node (LN), stomach, duodenum, ileum, and colon were sampled 73 days after transplantation (day +73), when the patient died from graft-vs-host disease. Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization (ISH) were used detect the HIV reservoir in tissues. CCR5 and CD3 expression in the LN was assessed using immunohistochemistry (IHC). Results. HIV DNA (vDNA) was detected in PBMCs by ddPCR pretransplant but not post-transplant. vDNA was detected by ISH in the rectum at days -8 and +22, and in the LN, colon, lung, and brain day +73. vDNA was also detected in the lung by ddPCR. IHC revealed CCR5+CD3+ cells in the LN postmortem. Conclusions. HIV was detected in multiple tissues 73 days after CCR5∆32 homozygous UCB allo-HCT despite myeloablative conditioning and complete donor marrow engraftment. These results highlight the importance of analyzing tissue during HIV cure interventions and inform the choice of assay used to detect HIV in tissue reservoirs.

Original languageEnglish (US)
JournalOpen Forum Infectious Diseases
Volume5
Issue number5
DOIs
StatePublished - May 1 2018

Bibliographical note

Funding Information:
Financial support. This work was supported by the following grants: National Institutes of Health grant numbers P01 CA65493 to M.R.V. and J.S.M., AI100879 to M.R.V., U19AI096109 and P01AI074340 to TWS RO1AI124965 to C.V.F. This work was also funded in part with federal funds from the National Cancer Institute, National Institutes of Health (Contract No. HHSN261200800001E to J.E.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Publisher Copyright:
© The Author(s) 2018.

Keywords

  • Allogeneic bone marrow transplantation
  • CCR5∆32
  • HIV cure
  • HIV reservoirs

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