Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7042, USA.
Curr Opin HIV AIDS. 2013 May;8(3):230-5. doi: 10.1097/COH.0b013e32835ef089.
A serious effort has begun to develop therapies that may be capable of eradicating established HIV infection in man. Because of the biological complexity of HIV infection that persists despite potent antiretroviral therapy, it is widely believed that if such therapies can be developed they will involve complex, multimodality approaches. We highlight some of the recent studies in this effort.
An inhibitor of histone deacetylase has been demonstrated to disrupt latency in man, and new histone deacetylase inhibitors have been identified. Other potential targets, such as histone methyltransferase, protein kinase C, and BRD4, have been recently studied. Model systems, both in primary cells and in animal models, are beginning to be validated. In the clinic, immune-based therapies to aid in the clearance of persistent infection are also being tested.
It is too early to know what combination eradication therapies for HIV infection will look like in the future, but candidate therapies and model systems to perform preclinical validation are beginning to take shape.
目前,人们已经开始认真努力地开发能够清除人体中已建立的 HIV 感染的疗法。由于 HIV 感染具有很强的抗逆转录病毒治疗的生物学复杂性,人们普遍认为,如果能够开发出这种疗法,它们将涉及复杂的多模式方法。我们强调了这方面的一些最新研究。
已经证明组蛋白去乙酰化酶抑制剂能够打破人类潜伏感染,并且已经发现了新的组蛋白去乙酰化酶抑制剂。其他潜在的靶点,如组蛋白甲基转移酶、蛋白激酶 C 和 BRD4,最近也有研究。在原代细胞和动物模型中,模型系统也开始得到验证。在临床上,也在测试免疫为基础的疗法以帮助清除持续性感染。
目前还很难知道未来针对 HIV 感染的联合清除疗法会是什么样子,但候选疗法和进行临床前验证的模型系统开始成形。