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Robust Closed-Loop Minimal Sampling Method for HIV Therapy Switching Strategies

机译:HIV疗法切换策略的鲁棒闭环最小抽样方法

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摘要

The emergence of drug-resistant strains of HIV during antiretroviral therapy is a major cause of treatment failure and disease progression. Development of a resistant strain necessitates switching to a new antiretroviral regimen composed of novel drugs. Recent work has shown that current methods of switching antiviral therapies carry significant unnecessary risk of subsequent failures, and optimal switching schedules to minimize this risk have been proposed. These switching schedules require frequent sampling of viral load during an induced phase of transient viral load reduction, with the goal of switching to the new antiviral regimen at an induced viral load minimum. The proposed frequent sampling carries an unacceptable level of cost both in terms of measurement expense and inconvenience to the patient. In this paper we propose a closed-loop sampling algorithm to reduce the number of samples required to achieve the desired reduction in risk. We demonstrate through Monte-Carlo analysis that the proposed method is able to robustly achieve an average 50% reduction in the number of required samples while maintaining a reduction in the risk of subsequent failure to under 3%, despite experimentally verified levels of model and measurement uncertainty.
机译:抗逆转录病毒治疗期间HIV耐药菌株的出现是治疗失败和疾病进展的主要原因。抗性应变的发展需要切换到由新型药物组成的新的抗逆转录病毒方案。最近的作品表明,目前的切换抗病毒治疗方法具有显着的后续故障的风险,并提出了最大限度地提高这种风险的最佳切换计划。这些切换时间表需要在瞬态病毒负荷减少诱导的阶段期间频繁采样病毒载量,其目的是在诱导的病毒载荷最小切换到新的抗病毒方案。建议的频繁采样在测量费用和患者的不便方面都具有不可接受的成本。在本文中,我们提出了一种闭环采样算法,以减少达到风险所需降低所需的样品数量。我们通过Monte-Carlo分析证明了所提出的方法能够强大地达到所需样本的数量的平均减少50%,同时保持随后失败的风险降低到3%以下的风险,尽管模型和测量水平降低了3%以下不确定。

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