Blood Journal
Leading the way in experimental and clinical research in hematology

Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation

  1. Kristina Allers1,
  2. Gero Hütter2,
  3. Jörg Hofmann3,
  4. Christoph Loddenkemper4,
  5. Kathrin Rieger2,
  6. Eckhard Thiel2, and
  7. Thomas Schneider1
  1. 1Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany;
  2. 2Department of Hematology, Oncology, and Transfusion Medicine, Medical Clinic III, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany;
  3. 3Institute of Medical Virology, Helmut-Ruska-Haus, Campus Mitte, Charité-University Medicine Berlin, Berlin, Germany; and
  4. 4Institute of Pathology/Research Center ImmunoSciences (RCIS), Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany

Abstract

HIV entry into CD4+ cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4+ T cells at the systemic level as well as in the gut mucosal immune system after CCR5Δ32/Δ32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4+ T cells contain a high proportion of activated memory CD4+ T cells, ie, the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells, indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.

  • Submitted September 23, 2010.
  • Accepted December 2, 2010.
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