Department of Pediatrics, University of California, San Diego and Rady Children's Hospital San Diego, La Jolla.
Division of Pediatric Infectious Diseases and Global Health, Department of Pediatrics, University of California, San Francisco.
J Pediatric Infect Dis Soc. 2020 Apr 30;9(2):159-165. doi: 10.1093/jpids/piy139.
P1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort.
The study enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to <18 years, with an HIV-1 RNA level ≥1000 copies/mL . Cumulative safety and HIV-1 RNA outcomes were assessed once the last enrolled participant reached 144 weeks of follow-up.
Among 23 adolescents enrolled, 16 remained in the study at least 144 weeks; the median follow-up was 153 weeks (range, 55-193 weeks). Dolutegravir was well tolerated, with grade 3 clinical adverse events in 5 participants, grade 3 laboratory abnormalities in 3, and grade 4 laboratory abnormalities in 1; none of the adverse events or abnormalities were judged to be treatment related. In an-intent-to-treat analysis, an HIV-1 RNA level <400 copies/mL at week 144 was achieved in 43% (10 of 23 participants; 95% confidence interval, 23.2%-65.5%); in addition, 35% (8 of 23; 16.4%-57.3%) had an HIV-1 RNA level <50 copies/mL. Nine participants (39%) discontinued study treatment before 144 weeks, but none because of adverse events or drug intolerance. All participants with sustained virologic control had excellent adherence; most who experienced virologic failure had adherence levels <90%. HIV-1 genotypic drug resistance testing was available at time of failure from 6 participants; 1 had evolution in integrase resistance with E138T, S147G, and R263K mutations at week 192 and phenotypic dolutegravir resistance of a 5.1-fold change.
Dolutegravir plus an optimized background regimen seemed safe, well tolerated, and efficacious in this cohort of treatment-experienced HIV-1-infected adolescents. Adherence remains problematic in this population.
NCT01302847.
P1093 是一项正在进行的 I/II 期多中心、开放性标签研究，评估多拉韦林联合优化背景治疗方案在年龄定义的儿科队列中的疗效；此处我们报道了年龄最大队列的长期安全性和病毒学疗效结果。
研究纳入了 12 至<18 岁、经治的人类免疫缺陷病毒 1 型（HIV-1）感染的青少年，HIV-1 RNA 水平≥1000 拷贝/ml。当最后入组的参与者随访 144 周时，评估累积安全性和 HIV-1 RNA 结果。
23 名青少年中，16 名至少随访 144 周，中位随访时间为 153 周（55-193 周）。多拉韦林耐受性良好，5 名参与者出现 3 级临床不良事件，3 名参与者出现 3 级实验室异常，1 名参与者出现 4 级实验室异常；均未判断为与治疗相关。在意向治疗分析中，23 名参与者中，有 43%（10/23）在第 144 周时 HIV-1 RNA<400 拷贝/ml（95%置信区间，23.2%-65.5%）；此外，35%（8/23）（16.4%-57.3%）HIV-1 RNA<50 拷贝/ml。9 名（39%）参与者在 144 周前停止研究治疗，但均非因不良事件或药物不耐受。所有维持病毒学控制的参与者均具有良好的依从性；大多数病毒学失败的参与者依从性水平<90%。在 6 名失败参与者中获得了失败时的 HIV-1 基因型耐药检测，其中 1 名在第 192 周时出现整合酶耐药，E138T、S147G 和 R263K 突变，以及表型多拉韦林耐药性为 5.1 倍变化。
在该经治的 HIV-1 感染青少年队列中，多拉韦林联合优化背景治疗方案似乎安全、耐受良好且有效。在该人群中，依从性仍然是个问题。
NCT01302847。
