Predictors of HIV Control after Antiretroviral Treatment Interruption

抗逆转录病毒疗法（ART）挽救了数百万人的生命，但也存在许多缺点，包括副作用、耐药性和负担能力。因此，艾滋病毒领域的一个高度优先事项是寻求消除或 控制细胞HIV储库，导致长期无ART HIV缓解。然而，一些挑战目前阻碍了我们设计和测试这种新疗法的能力。两个最重要的问题是：1）由于我们对HIV储库措施与治疗中断后病毒反弹动力学之间的关系的不完全理解，目前还不清楚早期干预性HIV储库试验的最佳替代终点应该是什么;和2）虽然有个体可以在ART中断后延迟/控制病毒血症，我们还没有确定其治疗后艾滋病毒控制的机制。通过拟议的研究，我们计划确定最能预测艾滋病毒反弹的关键病毒储库测量的组合，并深入了解治疗后控制者的显着队列背后的病毒学和免疫学机制。这些结果可能会加速对新型HIV疗法的评估，并为下一代HIV疗法确定新的靶点，重点是长期无药物HIV缓解。

DESCRIPTION (provided by applicant): Antiretroviral therapy (ART) has saved millions of lives, but is associated with numerous drawbacks including side-effects, drug resistance, and affordability. Thus, a high priority for the HIV field is the search for strategies to eliminate or control cellular HIV reservoirs, leading to long-term ART-free HIV remission. However, a number of challenges currently hinder our ability to design and test such novel therapies. Two of the most important problems are that: 1) It is unclear what the optimal surrogate endpoint should be for early-phase interventional HIV reservoir trials given our incomplete understanding of the relationship between HIV reservoir measures and the kinetics of viral rebound after treatment interruption; and 2) While there are individuals who can delay/control viremia after ART interruption, we have not yet identified the mechanisms underlying their post-treatment HIV control. Through the proposed studies, we plan to determine the combination of key viral reservoir measurements that best predict HIV rebound and provide an in-depth understanding of the virologic and immunologic mechanisms behind a remarkable cohort of post-treatment controllers. The results may accelerate the evaluation of novel HIV therapeutics and identify new targets for the next generation of HIV therapeutics focused on long-term drug-free HIV remission.