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Toward the Cure of HIV-1 Infection: Lessons Learned and Yet to be Learned as New Strategies are Developed.
AIDS Reviews ( IF 1.9 ) Pub Date : 2018-12-15 , DOI: 10.24875/aidsrev.18000027
Jeffrey M Jacobson 1, 2 , Kamel Khalili 1
Affiliation  

Here, we review the progress that has been made in achieving a cure of HIV-1 infection. To date, this has only occurred in one person after he received allogeneic stem cell transplants from a CCR5 ∆32 homozygous donor in addition to chemotherapy and radiation to treat his acute myelocytic leukemia. The general consensus is that achieving a sustained remission of infection in the absence of antiretroviral therapy will involve a combination of strategies that involve both the targeting of the latent proviral genome and the induction of more effective anti-HIV-1 immune responses. Efforts to reverse HIV-1 proviral DNA integration in the host cell genome and those to enhance anti-HIV immunity have been disappointing thus far. The lack of clinically validated assays to measure both effects has hampered the development of effective therapies. We suggest the consideration of genome editing as a new approach to reduce the latently integrated proviral genome. In addition, new approaches to therapeutic immunization, alterations of immunoregulatory pathways, anti-HIV-1 antibodies, and anti-HIV-1 chimeric antigen receptor T lymphocytes are in development.

中文翻译:

迈向治疗HIV-1感染:随着新战略的发展,经验教训尚待汲取。

在这里,我们回顾了在实现HIV-1感染治愈方面取得的进展。迄今为止,这种情况只发生在一个人,他接受了来自CCR5Δ32纯合供体的同种异体干细胞移植,此外还接受了化学疗法和放射线治疗他的急性粒细胞白血病。普遍的共识是,在没有抗逆转录病毒疗法的情况下实现感染的持续缓解将涉及多种策略的组合,这些策略既涉及靶向潜在的前病毒基因组,又涉及诱导更有效的抗HIV-1免疫应答。迄今为止,在宿主细胞基因组中逆转HIV-1前病毒DNA整合的努力以及增强抗HIV免疫力的努力都令人失望。缺乏可同时测量这两种作用的经过临床验证的测定法,阻碍了有效疗法的发展。我们建议考虑将基因组编辑作为减少潜在整合的原病毒基因组的新方法。另外,正在开发治疗免疫,改变免疫调节途径,抗HIV-1抗体和抗HIV-1嵌合抗原受体T淋巴细胞的新方法。
更新日期:2020-08-21
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