Predictors of HIV Control after Antiretroviral Treatment Interruption

描述(申请人提供)：抗逆转录病毒疗法(ART)拯救了数百万人的生命，但与许多缺点有关，包括副作用、耐药性和可负担性。因此，艾滋病毒领域的一个高度优先事项是寻找消除或 控制细胞艾滋病毒储存，导致长期无抗逆转录病毒药物的艾滋病毒缓解。然而，目前许多挑战阻碍了我们设计和测试这种新疗法的能力。其中最重要的两个问题是：1)鉴于我们对艾滋病毒储存措施与治疗中断后病毒反弹动力学之间的关系的不完全了解，尚不清楚早期干预性HIV储存试验的最佳替代终点应该是什么；2)虽然有些人可以在ART中断后延迟/控制病毒血症，但我们尚未确定他们治疗后控制艾滋病毒的机制。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库测量的组合，并提供对一批非凡的治疗后控制者背后的病毒学和免疫学机制的深入了解。这一结果可能会加速对新的艾滋病毒疗法的评估，并为专注于长期无药物的艾滋病毒缓解的下一代艾滋病毒疗法确定新的目标。

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.