在 3 个月至<11 岁的 HIV-1 感染婴儿和儿童中应用阿扎那韦粉剂和利托那韦的安全性和疗效：PRINCE-2 研究。

Safety and Efficacy of Atazanavir Powder and Ritonavir in HIV-1-Infected Infants and Children From 3 Months to <11 Years of Age: The PRINCE-2 Study.

机构信息

From the Children's Infectious Diseases Clinical Research Unit, Department of Pediatrics & Child Health, Stellenbosch University, Tygerberg, South Africa.

Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa.

出版信息

Pediatr Infect Dis J. 2018 Jun;37(6):e149-e156. doi: 10.1097/INF.0000000000001856.

DOI:10.1097/INF.0000000000001856

PMID:29206747

Abstract

BACKGROUND

Novel antiretroviral formulations that are palatable, safe, and effective are needed for infants and children.

METHODS

PRINCE-2 is an ongoing clinical trial assessing safety, efficacy, and palatability of once-daily atazanavir powder formulation boosted with ritonavir (ATV + RTV) plus optimized dual nucleos(t)ide reverse transcriptase inhibitors therapy in antiretroviral-naïve/experienced children with screening HIV-1 RNA ≥1000 copies/mL. Children 3 months to <11 years received ATV + RTV by 5 baseline weight bands: 5 to <10 kg = 150/80 mg; 5 to <10 kg = 200/80 mg; 10 to <15 kg = 200/80 mg; 15 to <25 kg = 250/80 mg; and 25 to <35 kg = 300/100 mg.

RESULTS

Of 99 treated children, 83.8% and 59.6% remained on ATV powder until 24 and 48 weeks, respectively. Through 48 weeks, the most common adverse events were upper respiratory tract infections (33.3%), gastroenteritis (28.3%), vomiting (21.2%) and hyperbilirubinemia (18.2%; none leading to treatment discontinuation). Serious adverse events occurred in 20.2% of patients. Laboratory grade 3-4 hyperbilirubinemia occurred in 9.2% and elevated total/pancreatic amylase in 33.7%/3.1%. At week 24, proportions with virologic suppression (HIV-1 RNA <50 copies/mL; intention-to-treat analysis) across weight bands were 10/23 (43.5%), 2/12 (16.5%), 10/21 (47.6%), 19/35 (54.3%) and 5/8 (62.5%), respectively. Virologic suppression was similar in antiretroviral-naïve/experienced patients and lowest in the 5 to <10 kg = 200/80 mg group, likely because of higher baseline HIV-1 RNA and discontinuation (66.7%). Overall, virologic suppression at weeks 24 (46.5%) and 48 (43.0%) was comparable. At week 48, 83.3% and 74.1% of caregivers reported no trouble giving ATV powder and RTV, respectively.

CONCLUSIONS

ATV powder palatability, efficacy and lack of unexpected safety findings support its use for HIV-1-infected children ≥3 months to <11 years.

摘要

背景

需要新型、口感好、安全且有效的抗逆转录病毒制剂，用于治疗婴儿和儿童。

方法

PRINCE-2 是一项正在进行的临床试验，评估每日一次阿扎那韦粉制剂联合利托那韦（ATV+RTV）强化治疗以及优化的双重核苷（酸）逆转录酶抑制剂治疗方案在抗逆转录病毒初治/经治、筛选 HIV-1 RNA≥1000 拷贝/ml 的儿童中的安全性、疗效和口感。3 个月至<11 岁的儿童根据 5 个基线体重组接受 ATV+RTV：体重<5-<10kg=150/80mg；体重<5-<10kg=200/80mg；体重 10-<15kg=200/80mg；体重 15-<25kg=250/80mg；体重 25-<35kg=300/100mg。

结果

99 例接受治疗的儿童中，83.8%和 59.6%的儿童分别在 24 周和 48 周时仍继续使用 ATV 粉。至 48 周时，最常见的不良事件为上呼吸道感染（33.3%）、胃肠炎（28.3%）、呕吐（21.2%）和高胆红素血症（18.2%；均无导致治疗中断）。20.2%的患者发生严重不良事件。9.2%的患者出现实验室检查 3-4 级高胆红素血症，33.7%的患者出现总/胰淀粉酶升高（3.1%）。24 周时，各体重组的病毒学抑制率（HIV-1 RNA<50 拷贝/ml；意向治疗分析）分别为：10/23（43.5%）、2/12（16.5%）、10/21（47.6%）、19/35（54.3%）和 5/8（62.5%）。初治/经治患者的病毒学抑制率相似，最低的是体重<5-<10kg=200/80mg 组（66.7%），可能是因为基线 HIV-1 RNA 较高且有患者停药。总体上，24 周（46.5%）和 48 周（43.0%）的病毒学抑制率相当。48 周时，83.3%和 74.1%的照护者报告称，给儿童服用 ATV 粉和 RTV 没有困难。