Background

Feasible, scalable, and cost-effective approaches to ensure virological suppression among children living with HIV are urgently needed. The aim of the Opt4Kids study was to determine the effect of point of care viral load and targeted drug resistance mutation testing in improving virological suppression among children on antiretroviral therapy (ART) in Kenya.

Methods

In this open-label, individually randomised controlled trial, we enrolled children living with HIV aged 1–14 years and who were either newly initiating or already receiving ART at five study facilities in Kenya. Participants were randomly allocated 1:1 to receive the intervention of point-of-care viral load testing every 3 months, targeted drug resistance mutation testing, and clinical decision support (point-of-care testing) or to receive the standard care (control group), stratified by facility site and age groups (1–9 years vs 10–14 years). Investigators were masked to the randomised group. The primary efficacy outcome was virological suppression (defined as a viral load of <1000 copies per mL) by point-of-care viral load testing at 12 months after enrolment in all participants with an assessment. This study is registered with ClinicalTrials.gov, NCT03820323.

Findings

Between March 7, 2019, and December 31, 2020, we enrolled 704 participants. Median age at enrolment was 9 years (IQR 7–12), 344 (49%) participants were female and 360 (51%) were male, and median time on ART was 5·8 years (IQR 3·1–8·6). 536 (76%) of 704 had documented virological suppression at enrolment. At 12 months after enrolment, the proportion of participants achieving virological suppression in the intervention group (283 [90%] of 313 participants with a 12 month point-of-care viral load test) did not differ from that in the control group (289 [92%] of 315; risk ratio [RR] 0·99, 95% CI 0·94–1·03; p=0·55). We identified 138 episodes of viraemia in intervention participants, of which 107 (89%) samples successfully underwent drug resistance mutation testing and 91 (85%) had major drug resistance mutations. The median turnaround time for viral load results was 1 day (IQR 0–1) in the intervention group and 15 days (10–21) in the control group.

Interpretation

Point-of-care viral load testing decreased turnaround time and targeted drug resistance mutation testing identified a high prevalence of HIV drug resistance mutations in children living with HIV, but the combined approach did not increase rates of virological suppression. Further research in combination interventions, including point-of-care viral load and drug resistance mutation testing coupled with psychosocial support, is needed to optimise virological suppression for children living with HIV.

Funding

National Institutes of Mental Health of the US National Institutes of Health, Thrasher Research Fund.

中文翻译：

---

肯尼亚儿童抗逆转录病毒治疗的护理点 HIV 病毒载量和靶向耐药突变检测与标准护理 (Opt4Kids)：一项开放标签、随机对照试验

背景

迫切需要采取可行、可扩展且具有成本效益的方法来确保艾滋病毒感染儿童的病毒学抑制。Opt4Kids 研究的目的是确定床边病毒载量和靶向耐药突变检测对肯尼亚接受抗逆转录病毒治疗 (ART) 的儿童改善病毒学抑制的效果。

方法

在这项开放标签、单独随机对照试验中，我们在肯尼亚的五个研究机构招募了 1-14 岁的艾滋病毒感染者，这些儿童要么刚刚开始接受抗逆转录病毒治疗，要么已经接受了抗逆转录病毒治疗。参与者以 1:1 的比例随机分配，接受每 3 个月一次的床旁病毒载量检测、靶向耐药突变检测和临床决策支持（床旁检测）干预，或接受标准护理（对照）组），按设施地点和年龄组（1-9 岁vs 10-14 岁）分层。研究人员被随机分组​​。主要疗效结果是在所有参与者入组并进行评估后 12 个月进行即时病毒载量测试，以实现病毒学抑制（定义为病毒载量<1000 拷贝/毫升）。本研究已在 ClinicalTrials.gov 注册，NCT03820323。

发现

2019年3月7日至2020年12月31日期间，我们招募了704名参与者。入组时的中位年龄为 9 岁 (IQR 7–12)，344 名 (49%) 参与者为女性，360 名 (51%) 为男性，接受 ART 的中位时间为 5·8 年 (IQR 3·1–8·6) ）。704 人中有 536 人（76%）在入组时记录了病毒学抑制情况。入组后 12 个月时，干预组中实现病毒学抑制的参与者比例（313 名参与者中进行了 12 个月即时病毒载量测试的 283 名参与者 [90%]）与对照组（289 名参与者）没有差异。 [92%]（共 315 名）；风险比 [RR] 0·99，95% CI 0·94–1·03；p=0·55）。我们在干预参与者中发现了 138 例病毒血症，其中 107 例（89%）样本成功进行了耐药突变检测，91 例（85%）出现了主要耐药突变。干预组病毒载量结果的中位周转时间为 1 天 (IQR 0-1)，对照组为 15 天 (10-21)。

解释

护理点病毒载量检测缩短了周转时间，并且有针对性的耐药突变检测发现艾滋病毒感染儿童中艾滋病毒耐药突变的患病率很高，但综合方法并没有增加病毒学抑制率。需要对组合干预措施进行进一步研究，包括即时病毒载量和耐药突变检测以及社会心理支持，以优化艾滋病毒感染儿童的病毒学抑制。

资金

美国国立卫生研究院国家心理健康研究所 Thrasher 研究基金。