Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.
Blood. 2011 Mar 10;117(10):2791-9. doi: 10.1182/blood-2010-09-309591. Epub 2010 Dec 8.
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.
HIV 进入 CD4(+) 细胞需要与细胞受体相互作用，通常是 CCR5 或 CXCR4。我们之前曾报道过一例 HIV 感染患者，在接受 CCR5Δ32/Δ32 干细胞移植后停止抗逆转录病毒治疗，但病毒复制仍然不存在。然而，人们预计长期存在的病毒库会在免疫重建过程中导致 HIV 反弹和疾病进展。在本研究中，我们证明了在 CCR5Δ32/Δ32 干细胞移植后，系统性和肠道黏膜免疫系统中的 CD4(+) T 细胞成功重建，而患者仍然没有任何 HIV 感染的迹象。尽管恢复的 CD4(+) T 细胞含有大量活化的记忆 CD4(+) T 细胞，即 HIV 的优先靶标，并且容易被 CXCR4 嗜性 HIV 进行有效感染，但仍观察到这种情况。此外，在免疫重建过程中，我们发现了宿主组织细胞被供体衍生细胞替代的证据，表明病毒库的大小随着时间的推移而减少。总之，我们的结果强烈表明，该患者已实现 HIV 的治愈。
