BACKGROUND For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value. METHODS We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%). We assumed 50% of children who had viraemia after abacavir-lamivudine exposure had NRTI resistance; with resistance, we assumed zidovudine-lamivudine-dolutegravir was more effective than abacavir-lamivudine-dolutegravir. We designated a strategy as preferred if it was most effective and least costly or had an incremental cost-effectiveness ratio less than half the South African 2020 gross domestic product per capita. FINDINGS Under base-case assumptions, the viral load plus dolutegravir strategy would be the most effective (projected undiscounted life expectancy of 39·72 life-years) and least costly strategy (US$24 600 per person); the no dolutegravir strategy was the least effective (34·49 life-years) and most expensive ($26 480 per person). In sensitivity analyses, the 24-week virological suppression probability and subsequent monthly virological failure risks (ie, late failure) were most influential on cost-effectiveness. Only with a high late-failure risk for zidovudine-lamivudine-dolutegravir (ie, ≥0·3% per month in the base case or >0·5% per month if abacavir also confers low virological suppression probability in the presence of NRTI resistance [65%]) would the dolutegravir strategy become preferred above the viral load plus dolutegravir strategy. INTERPRETATION For programmes transitioning to dolutegravir-based regimens, our model predicted that doing so would be more effective and less costly than continuing current ART regimens, regardless of NRTI choice. Whether viral load testing for children with HIV is necessary to inform NRTI choice depends substantially on the comparative outcomes of abacavir and zidovudine after switching to dolutegravir-containing ART. FUNDING The Eunice Kennedy Shriver Institute for Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the Massachusetts General Hospital Executive Committee on Research, the Massachusetts General Hospital, and the Medical Research Council.

中文翻译：

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在南非，病毒载量检测将有抗逆转录病毒治疗经验的儿童过渡到多替拉韦的成本效益：建模分析。


背景 对于接受抗逆转录病毒治疗 （ART） 的 HIV 感染儿童，建议过渡到含多替拉韦的方案。本研究的目的是评估引入病毒载量检测以告知 HIV 和病毒血症儿童的新核苷或核苷酸逆转录酶抑制剂 （NRTI） 以及基于多替拉韦的 ART 是否有益且具有良好的经济价值。方法 我们使用预防艾滋病并发症的成本效益-儿科模型来预测三种策略的临床和成本影响，这些策略在接受阿巴卡韦-拉米夫定-依非韦伦的 8 岁南非 HIV 儿童模拟队列中：（1） 继续目前的 ART（无多替拉韦;阿巴卡韦-拉米夫定-依非韦伦）;（2） 将所有 HIV 感染儿童过渡到多替拉韦，保持当前的 NRTIs（多替拉韦;阿巴卡韦-拉米夫定-多替拉韦）;或 （3） 根据病毒载量检测（病毒载量加多替拉韦）过渡到多替拉韦，如果病毒学抑制，则保持当前的 NRTI（阿巴卡韦-拉米夫定-多替拉韦，队列的 70%），或者如果病毒血症，将阿巴卡韦转换为齐多夫定（齐多夫定-拉米夫定-多替拉韦，30%）。我们假设 50% 的阿巴卡韦-拉米夫定暴露后出现病毒血症的儿童具有 NRTI 耐药性;在耐药性方面，我们假设齐多夫定-拉米夫定-多替拉韦比阿巴卡韦-拉米夫定-多替拉韦更有效。如果策略最有效且成本最低，或者增量成本效益比低于南非 2020 年人均国内生产总值的一半，我们将该策略指定为首选策略。 发现 在基本假设下，病毒载量加多替拉韦策略将是最有效的（预计未贴现的预期寿命为 39·72 生命年）和成本最低的策略（每人 24 600 美元）;不使用多替拉韦策略效果最差（34·49 生命年）和最昂贵（每人 26 480 美元）。在敏感性分析中，24 周病毒学抑制概率和随后的每月病毒学失败风险 （即晚期失败） 对成本效益影响最大。只有在齐多夫定-拉米夫定-多替拉韦的晚期失败风险较高（即，在基本情况下每月 ≥0·3%，或者如果阿巴卡韦在 NRTI 耐药性存在的情况下也赋予较低的病毒学抑制概率，则每月 >0·5% [65%]），多替拉韦策略才会成为优于病毒载量加多替拉韦策略的首选。解释 对于过渡到基于多替拉韦的方案的计划，我们的模型预测，无论 NRTI 选择如何，这样做都会比继续当前的 ART 方案更有效且成本更低。是否需要对 HIV 感染儿童进行病毒载量检测以告知 NRTI 的选择，在很大程度上取决于改用含多替拉韦的 ART 后阿巴卡韦和齐多夫定的比较结局。资助 Eunice Kennedy Shriver 儿童健康与人类发展研究所、国家过敏和传染病研究所、马萨诸塞州总医院研究执行委员会、马萨诸塞州总医院和医学研究委员会。