From the Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) at Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
Pediatr Infect Dis J. 2023 Jul 1;42(7):576-581. doi: 10.1097/INF.0000000000003878. Epub 2023 Feb 14.
Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs).
Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS).
Among 9419 CALHIV using DTG, 7898 had a documented post-DTG VL, and VLS post-DTG was 93.4% (7378/7898). VLS for antiretroviral therapy (ART) initiations was 92.4% (246/263), and VLS was maintained for the ART-experienced [92.9% (7026/7560) pre- vs. 93.5% (7071/7560) post-DTG; P = 0.14). Among previously unsuppressed, 79.8% (426/534) achieved VLS with DTG. Only 5 patients reported a Grade 3 or 4 adverse event (0.057 per 100 patient-years) requiring DTG discontinuation. History of protease inhibitor-based ART [odds ratio (OR) = 1.53; 95% confidence interval (CI): 1.16-2.03], care in Tanzania (OR = 5.45; 95% CI: 3.41-8.70), and being 15-19 years old (OR = 1.31; 95% CI: 1.03-1.65) were associated with gain of VLS post-DTG. Predictors of VLS on DTG included VLS before DTG (OR = 3.87; 95% CI: 3.03-4.95) and using the once-daily, single tab tenofovir-lamivudine-DTG regimen (OR = 1.78; 95% CI: 1.43-2.22). SDS maintained VLS [95.9% (2032/2120) pre- vs. 95.0% (2014/2120) post-SDS with DTG; P = 0.19], and 83.0% (73/88) of unsuppressed gained VLS using SDS with DTG.
We found DTG to be highly effective and safe within our cohort of CALHIV in LMICs. These findings can empower clinicians to prescribe DTG confidently to eligible CALHIV.
尽管临床试验和高收入国家取得了令人鼓舞的结果，但在中低收入国家（LMICs），缺乏有关多替拉韦（DTG）在感染艾滋病毒的儿童和青少年（CALHIV）中的有效性和安全性的大规模数据。
对 2017 年至 2020 年期间在博茨瓦纳、斯威士兰、莱索托、马拉维、坦桑尼亚和乌干达的 9419 名接受 DTG 治疗的体重≥20kg 的 0-19 岁 CALHIV 进行回顾性分析，以确定 DTG 治疗 CALHIV 的有效性、安全性和病毒载量抑制（VLS）的预测因素，包括通过单一药物替换（SDS）。
在接受 DTG 治疗的 9419 名 CALHIV 中，有 7898 名的 DTG 后 VL 记录，DTG 后 VLS 为 93.4%（7378/7898）。ART 启动时的 VLS 为 92.4%（246/263），ART 经验者的 VLS 得以维持[92.9%（7026/7560）前 vs. 93.5%（7071/7560）后 DTG；P=0.14）。在以前未得到抑制的患者中，79.8%（426/534）通过 DTG 实现了 VLS。仅 5 名患者报告了 3 级或 4 级不良事件（每 100 患者年 0.057 次），需要停用 DTG。基于蛋白酶抑制剂的 ART 史（比值比[OR] = 1.53；95%置信区间[CI]：1.16-2.03）、在坦桑尼亚接受治疗（OR = 5.45；95%CI：3.41-8.70）和年龄在 15-19 岁（OR = 1.31；95%CI：1.03-1.65）与 DTG 后 VLS 的获得相关。DTG 上 VLS 的预测因素包括 DTG 前的 VLS（OR = 3.87；95%CI：3.03-4.95）和使用每日一次、单一片剂替诺福韦-拉米夫定-DTG 方案（OR = 1.78；95%CI：1.43-2.22）。SDS 维持了 VLS[95.9%（2032/2120）前 vs. 95.0%（2014/2120）后 DTG；P=0.19]，并使用 DTG 进行 SDS 治疗的 83.0%（73/88）未得到抑制的患者获得了 VLS。
我们发现 DTG 在我们的中低收入国家的 CALHIV 队列中具有高度有效性和安全性。这些发现可以使临床医生有信心为符合条件的 CALHIV 开具 DTG 处方。
