Evidence for the cure of HIV infection by CCR5 – 32 stem cell transplantation

Kristina Allers,*, Gero Hütter, Jörg Hofmann, Christoph Loddenkemper, Kathrin Rieger, Eckhard Thiel and Thomas Schneider

Dec 2: Timothy Ray Brown can personally affirm that stem cells cure HIV disease, according to a December 2 report in the journal BLOOD. Mr. Brown, an HIV-positive American living in Germany, had leukemia and underwent chemotherapy and bone marrow transplantation in Berlin in 2007. His bone marrow match carried a rare gene mutation in the CCR5 receptor protein, rendering the transplanted cells resistant to HIV infection. Twenty months following the bone marrow transplant, the German team reported Mr. Brown’s leukemia appeared cured, and there was no evidence of HIV in his blood even though he had stopped his antiviral medication prior to the bone marrow transplant.

Now, a year later, the German team has re-examined Mr. Brown’s immune system for evidence of latent HIV infected cells, and found none. The uninfected transplanted bone marrow cells have replaced immune cells in all the parts of Mr. Brown’s body examined. This evidence is consistent with a cure of his HIV disease. Blood, Journal of the American Society of Hematology

This promising proof-of-principle success provides additional support for the patient-specific stem cell based therapy described in Bedford’s June Science Highlights.

ARTICLE 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 CCR5{Delta}32/{Delta}32 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 following CCR5{Delta}32/{Delta}32 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, i.e. 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.



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