One approach to 'functional cure' of HIV infection is to induce durable control of HIV replication after the interruption of antiretroviral therapy (ART). However, the major factors that determine the viral 'setpoint' level after treatment interruption are not well understood. Here we combine data on ART interruption following SIV infection for 124 total animals from 10 independent studies across 3 institutional cohorts to understand the dynamics and predictors of post-treatment viral control. We find that the timing of treatment initiation is an important determinant of both the peak and early setpoint viral levels after treatment interruption. During the first 3 weeks of infection, every day of delay in treatment initiation is associated with a 0.22 log10 copies/ml decrease in post-rebound peak and setpoint viral levels. However, delay in initiation of ART beyond 3 weeks of infection is associated with higher post-rebound setpoint viral levels. For animals treated beyond 3 weeks post-infection, viral load at ART initiation was the primary predictor of post-rebound setpoint viral levels. Potential alternative predictors of post-rebound setpoint viral loads including cell-associated DNA or RNA, time from treatment interruption to rebound, and pre-interruption CD8+ T cell responses were also examined in the studies where these data were available. This analysis suggests that optimal timing of treatment initiation may be an important determinant of post-treatment control of HIV.

中文翻译：

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抗逆转录病毒治疗的开始时间可预测治疗后 SIV 复制的控制。

HIV感染“功能性治愈”的一种方法是在抗逆转录病毒治疗（ART）中断后诱导对HIV复制的持久控制。然而，决定治疗中断后病毒“设定值”水平的主要因素尚不清楚。在这里，我们结合了来自 3 个机构队列的 10 项独立研究的 124 只动物 SIV 感染后 ART 中断的数据，以了解治疗后病毒控制的动态和预测因素。我们发现，治疗开始的时间是治疗中断后病毒水平峰值和早期设定值的重要决定因素。在感染的前 3 周内，治疗开始每延迟一天，反弹后峰值和设定点病毒水平就会减少 0.22 log10 拷贝/ml。然而，感染后 3 周之后才开始 ART 与较高的反弹后设定点病毒水平有关。对于感染后 3 周以上接受治疗的动物，开始 ART 时的病毒载量是反弹后设定点病毒水平的主要预测因子。在可获得这些数据的研究中，还检查了反弹后设定点病毒载量的潜在替代预测因子，包括细胞相关 DNA 或 RNA、从治疗中断到反弹的时间以及中断前 CD8+ T 细胞反应。该分析表明，治疗开始的最佳时机可能是治疗后艾滋病毒控制的重要决定因素。