Saez-Llorens Xavier, Violari Avy, Ndiweni Dalubuhle, Yogev Ram, Cashat Miguel, Wiznia Andrew, Chittick Greg, Harris Jeanette, Hinkle John, Blum M Robert, Adda Nathalie, Rousseau Franck
Infectious Disease Department, Hospital del Nino, Panama City, Panama.
Pediatrics. 2008 Apr;121(4):e827-35. doi: 10.1542/peds.2006-3078. Epub 2008 Mar 10.
The purpose of this work was to obtain long-term safety and efficacy data for antiretroviral regimens containing emtricitabine in HIV-infected pediatric subjects and confirm that a pediatric dose of 6 mg/kg once daily would provide steady-state emtricitabine concentrations comparable to those observed in adults given 200 mg of emtricitabine once daily.
HIV-infected subjects between 3 months and 16 years of age were enrolled, including 71 antiretroviral-naïve subjects and 45 antiretroviral-experienced subjects. Naive subjects received emtricitabine plus stavudine plus lopinavir or ritonavir. Experienced subjects replaced the lamivudine in their existing regimens with emtricitabine. Tolerance, safety, disease progression, and virologic and immunologic responses were evaluated.
The Kaplan-Meier probability of persistent virologic response in the intent-to-treat population through week 164 at < or = 400 copies per mL and < or = 50 copies per mL was 74% and 62%, respectively. Three subjects (3%) discontinued the study for adverse events, 8 (7%) for virologic failure, and 1 died through a median follow-up of 164 weeks. The annualized incidence rate of grade 3 to 4 adverse events and grade 3 to 4 laboratory abnormalities was 6% and 3%, respectively. The annualized incidence rate of serious adverse events was 9%, with 1% attributed as related to emtricitabine. Genotypic analysis showed the emergence of the M184V mutation in 4 of the 15 subjects who experienced virologic failure through week 164. Pharmacokinetic evaluation demonstrated plasma drug exposures in these children comparable to adults receiving the approved dose of 200 mg once daily.
These results demonstrate the safety and efficacy of emtricitabine in pediatric patients. They also support that the safety and efficacy profile of emtricitabine in children is similar to that demonstrated in adults.
本研究旨在获取含恩曲他滨的抗逆转录病毒方案在HIV感染儿科受试者中的长期安全性和疗效数据，并确认每日一次6mg/kg的儿科剂量能使恩曲他滨稳态血药浓度与成人每日一次服用200mg恩曲他滨时所观察到的浓度相当。
纳入3个月至16岁的HIV感染受试者，其中包括71例初治抗逆转录病毒治疗受试者和45例经治抗逆转录病毒治疗受试者。初治受试者接受恩曲他滨加司他夫定加拉替拉韦或利托那韦治疗。经治受试者用恩曲他滨替代其现有方案中的拉米夫定。评估耐受性、安全性、疾病进展以及病毒学和免疫学反应。
在意向性治疗人群中，至第164周时，每毫升低于或等于400拷贝以及低于或等于50拷贝的持续病毒学应答的Kaplan-Meier概率分别为74%和62%。3名受试者（3%）因不良事件退出研究，8名（7%）因病毒学失败退出，中位随访164周期间有1例死亡。3至4级不良事件和3至4级实验室异常的年化发生率分别为6%和3%。严重不良事件的年化发生率为9%，其中1%归因于恩曲他滨。基因分析显示，在第164周时出现病毒学失败的15名受试者中有4名出现了M184V突变。药代动力学评估表明，这些儿童的血浆药物暴露量与接受每日一次200mg批准剂量的成人相当。
这些结果证明了恩曲他滨在儿科患者中的安全性和疗效。它们还支持恩曲他滨在儿童中的安全性和疗效特征与在成人中所显示的相似。
