title: Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation.
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.
authors.affiliation: Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany. kristina.allers@charite.de
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.forename: Gero
authors.initials: G
authors.lastname: Hütter
authors.forename: Jörg
authors.initials: J
authors.lastname: Hofmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rieger
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000628:therapy; D019713:Receptors, CCR5 / Q000235:genetics*; D033581:Stem Cell Transplantation / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D019713:Receptors, CCR5