Thresholds for post-rebound SHIV control after CCR5 gene-edited autologous hematopoietic cell transplantation

Elife. 2021 Jan 12;10:e57646. doi: 10.7554/eLife.57646.


Autologous, CCR5 gene-edited hematopoietic stem and progenitor cell (HSPC) transplantation is a promising strategy for achieving HIV remission. However, only a fraction of HSPCs can be edited ex vivo to provide protection against infection. To project the thresholds of CCR5-edition necessary for HIV remission, we developed a mathematical model that recapitulates blood T cell reconstitution and plasma simian-HIV (SHIV) dynamics from SHIV-1157ipd3N4-infected pig-tailed macaques that underwent autologous transplantation with CCR5 gene editing. The model predicts that viral control can be obtained following analytical treatment interruption (ATI) when: (1) transplanted HSPCs are at least fivefold higher than residual endogenous HSPCs after total body irradiation and (2) the fraction of protected HSPCs in the transplant achieves a threshold (76-94%) sufficient to overcome transplantation-dependent loss of SHIV immunity. Under these conditions, if ATI is withheld until transplanted gene-modified cells engraft and reconstitute to a steady state, spontaneous viral control is projected to occur.

Keywords: HIV cure; autologous transplantation; computational biology; hematopoietic ΔCCR5 stem cells; infectious disease; mathematical modeling; microbiology; nonlinear mixed-effects; pigtailed macaque; systems biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Editing*
  • HIV / physiology*
  • Hematopoietic Stem Cell Transplantation*
  • Macaca nemestrina
  • Receptors, CCR5 / genetics*
  • Simian Immunodeficiency Virus / physiology*
  • Transplantation, Autologous


  • CCR5 protein, human
  • Receptors, CCR5