Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUC) and concentration at the end of the dosing interval (C) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with , . Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUC for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7–119·7); C was 34·6% lower than adults (65·4%, 49·1–87·2). Both parameters were within the target exposure range previously found in adults, children, or both”. Grade 3–4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3–4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. Gilead Sciences.

中文翻译：

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比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺联合制剂在 2 岁及以上 HIV 病毒学抑制儿童中的药代动力学和安全性：一项 2/3 期、开放标签、单臂研究


比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺复合制剂是一种单片疗法，在一项为期 48 周的 2/3 期试验中，对感染 HIV 的儿童和青少年（6 岁至 <18 岁）有效且耐受性良好。在这项研究中，我们报告了 2 岁以上、体重 14 公斤至 25 公斤以下儿童的数据。我们在南非、泰国、乌干达和美国进行了这项开放标签、多中心、多队列、单臂研究。参与者是病毒学受到抑制的艾滋病毒儿童，年龄至少 2 岁，体重 14 公斤至 25 公斤以下。参与者每天一次接受比克替拉韦（30 mg）、恩曲他滨（120 mg）和替诺福韦艾拉酚胺（15 mg）治疗，体重达到至少25公斤。该研究包括第 2 周的药代动力学评估，通过与之前的成人数据进行比较，确认该体重范围内联合配方的比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺的剂量。主要结局为比克替拉韦第 2 周的给药间隔曲线下面积 (AUC) 和给药间隔结束时的浓度 (C)，以及截至第 24 周结束时治疗中出现的不良事件和实验室异常的发生率接受至少一剂比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺的参与者。这项研究已在 注册。总体而言，22 名参与者接受了筛查（从 2018 年 11 月 14 日到 2020 年 1 月 11 日），完成了比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺的治疗（直到第 48 周），并进入延长阶段。 比克替拉韦 AUC 的几何最小二乘均值 (GLSM) 比率比成人高 7·6%（GLSM 比率 107·6%，90% CI 96·7–119·7）； C 比成人低 34·6%（65·4%、49·1–87·2）。这两个参数都在之前针对成人、儿童或两者的目标暴露范围内”。到第 24 周结束时，四名参与者 (18%) 出现 3-4 级实验室异常，到第 48 周结束时，有 6 名参与者 (27%) 出现 3-4 级实验室异常。到本周末，三名参与者 (14%) 出现药物相关不良事件24 和 48 周；没有一个是严重的。到第 24 周和第 48 周结束时，没有发生 3-4 级不良事件、严重不良事件或导致停药的不良事件。数据支持使用单片联合配方比克替拉韦 (30 mg)、恩曲他滨 (120 mg)、替诺福韦艾拉酚胺（15 毫克）用于治疗 2 岁以上且体重 14 公斤至 25 公斤以下儿童的艾滋病毒。吉利德科学。