Journal of The Royal Society Interface ( IF 3.9 ) Pub Date : 2021-04-14 , DOI: 10.1098/rsif.2020.1015 Jessica M Conway 1 , Paige Meily 2 , Jonathan Z Li 3 , Alan S Perelson 4
Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Typically suspension of therapy is rapidly followed by rebound of viral loads to high, pre-therapy levels. Indeed, a recent study showed that approximately 90% of treatment interruption study participants show viral rebound within at most a few months of therapy suspension, but the remaining 10%, showed viral rebound some months, or years, after ART suspension. Some may even never rebound. We investigate and compare branching process models aimed at gaining insight into these viral dynamics. Specifically, we provide a theory that explains both short- and long-term viral rebounds, and post-treatment control, via a multitype branching process with time-inhomogeneous rates, validated with data from Li et al. (Li et al. 2016 AIDS30, 343–353. (doi:10.1097/QAD.0000000000000953)). We discuss the associated biological interpretation and implications of our best-fit model. To test the effectiveness of an experimental intervention in delaying or preventing rebound, the standard practice is to suspend therapy and monitor the study participants for rebound. We close with a discussion of an important application of our modelling in the design of such clinical trials.
中文翻译:
用于临床试验计划的短期和长期 HIV 病毒反弹的统一模型
抗逆转录病毒疗法 (ART) 可有效控制 HIV 感染,抑制 HIV 病毒载量。通常暂停治疗后病毒载量迅速反弹至治疗前的高水平。事实上,最近的一项研究表明,大约 90% 的治疗中断研究参与者在治疗暂停后最多几个月内出现病毒反弹,但其余 10% 在 ART 暂停后几个月或几年出现病毒反弹。有些甚至可能永远不会反弹。我们调查和比较旨在深入了解这些病毒动态的分支过程模型。具体来说,我们提供了一个理论,通过具有时间不均匀率的多类型分支过程来解释短期和长期病毒反弹以及治疗后控制,并通过 Li等人的数据进行验证。(李等。2016 AIDS 30,343-353。(doi:10.1097/QAD.0000000000000953))。我们讨论了我们的最佳拟合模型的相关生物学解释和含义。为了测试实验干预在延迟或预防反弹方面的有效性,标准做法是暂停治疗并监测研究参与者的反弹。我们最后讨论了我们的模型在此类临床试验设计中的重要应用。