Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
J Pediatric Infect Dis Soc. 2023 Dec 16;12(12):602-609. doi: 10.1093/jpids/piad078.
IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.
Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations.
A total of 45 adolescents, median age 15 (range, 12-17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4-99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6-98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths.
We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.
IMPACT 2014 研究是一项 I/II 期、多中心、开放性、非随机研究，评估多拉韦林（DOR）与拉米夫定（3TC）和富马酸替诺福韦二吡呋酯（TDF）组成的固定剂量复方（DOR FDC）在 HIV-1 青少年中的疗效、安全性和耐受性。我们报告了通过 96 周时 DOR FDC 的疗效、安全性和耐受性。
参与者为年龄在 12 至<18 岁、体重至少 45kg、且无抗逆转录病毒（ARV）治疗史或病毒学抑制但无记录的 DOR/3TC/TDF 耐药突变的青少年。疗效终点为使用观察失败法在第 48 周和第 96 周评估的 HIV-1 RNA<40 拷贝/ml 的参与者比例。安全性和耐受性结局为不良事件（AE）和治疗中断的发生率。
共有 45 名青少年（中位年龄 15 岁[范围，12-17 岁]；58%女性）入组，其中 2 名（4.4%）为 ARV 初治者。在 45 名参与者中，42 名（93.3%）完成了研究，41 名（91.1%）完成了研究治疗。第 48 周时，41/42 名（97.6%；95%置信区间[CI]，87.4-99.9）和第 96 周时，37/40 名（92.5%；95%CI，79.6-98.4）参与者实现或维持了 HIV-1 RNA<40 拷贝/ml。无因 AE 导致的治疗相关停药，且无药物相关的≥3 级 AE 或死亡。
我们发现，对于 HIV-1 青少年患者，每日一次 DOR FDC 治疗方案安全且耐受良好，可维持病毒抑制 96 周。
