McKinney Ross E, Rodman John, Hu Chengcheng, Britto Paula, Hughes Michael, Smith Mary Elizabeth, Serchuck Leslie K, Kraimer Joyce, Ortiz Alberto A, Flynn Patricia, Yogev Ram, Spector Stephen, Draper Linda, Tran Paul, Scites Melissa, Dickover Ruth, Weinberg Adriana, Cunningham Coleen, Abrams Elaine, Blum M Robert, Chittick Gregory E, Reynolds Laurie, Rathore Mobeen
Department of Pediatrics, Duke University Medical Center, Box 3461, Durham, NC 27710, USA.
Pediatrics. 2007 Aug;120(2):e416-23. doi: 10.1542/peds.2006-0925. Epub 2007 Jul 23.
Compliance with complex antiretroviral therapy regimens is a problem for HIV-1-infected children and their families. Simple, safe, and effective regimens are important for long-term therapeutic success.
A novel, once-daily dosing regimen of 3 antiretroviral drugs, emtricitabine, didanosine, and efavirenz, was tested in 37 therapy-naive HIV-infected children and adolescents between 3 and 21 years of age (inclusive). Subjects were followed for > or = 96 weeks on an intention-to-treat basis. Signs, symptoms, plasma HIV-1 RNA viral load, CD4 counts, and safety laboratories were followed regularly. End points were the proportion of subjects with plasma HIV < 400 or 50 HIV copies per mL and safety and tolerability of the regimen.
Thirty-seven subjects enrolled at 16 sites. Two subjects with rashes during the first 2 weeks of therapy were the only adverse events leading to study-drug discontinuation. Other early (before protocol-scheduled conclusion) study discontinuations included 3 viral failures on treatment and 5 patients who stopped therapy for apparently nonmedical reasons. Possible drug-related adverse events included 1 grade 4 low-glucose and 5 varied grade 3 events. There were no deaths. Virologic outcomes demonstrated that 32 (85%) of 37 subjects achieved viral suppression to < 400 RNA copies per mL, and 26 (72%) of 37 subjects maintained sustained suppression at < 50 copies per mL through week 96. The median baseline CD4 count was 310 per microL (17%), which increased at week 96 by a median of +329 cells per microL (by +18% CD4). Pharmacokinetic results were as predicted for emtricitabine, didanosine, and efavirenz capsules, whereas efavirenz concentrations in children receiving efavirenz oral solution were lower than anticipated, requiring a dose escalation after the planned assessment point.
A once-daily regimen of emtricitabine, didanosine, and efavirenz proved to be safe and tolerable and demonstrated good immunologic and virologic efficacy in this 2-year study.
对于感染人类免疫缺陷病毒1型（HIV-1）的儿童及其家庭而言，坚持复杂的抗逆转录病毒治疗方案是一个难题。简单、安全且有效的治疗方案对于长期治疗成功至关重要。
在37名年龄在3至21岁（含）之间、未接受过治疗的HIV感染儿童和青少年中，测试了一种新型的每日一次给药方案，该方案包含三种抗逆转录病毒药物：恩曲他滨、去羟肌苷和依非韦伦。在意向性治疗的基础上，对受试者进行了≥96周的随访。定期跟踪体征、症状、血浆HIV-1 RNA病毒载量、CD4细胞计数以及安全性实验室指标。终点指标为血浆HIV低于每毫升400拷贝或50拷贝的受试者比例以及该治疗方案的安全性和耐受性。
16个研究点共纳入37名受试者。在治疗的前2周内，有2名出现皮疹的受试者是导致停用研究药物的唯一不良事件。其他早期（在方案预定结束之前）研究终止情况包括3例治疗中的病毒学失败以及5名因明显非医学原因停止治疗的患者。可能与药物相关的不良事件包括1例4级低血糖和5例不同的3级事件。无死亡病例。病毒学结果显示，37名受试者中有32名（85%）实现了病毒抑制，病毒载量低于每毫升400拷贝，37名受试者中有26名（72%）在第96周时维持病毒载量持续抑制在每毫升50拷贝以下。基线CD4细胞计数中位数为每微升310个（17%），在第96周时中位数增加了每微升329个细胞（CD4增加了18%）。药代动力学结果与恩曲他滨、去羟肌苷和依非韦伦胶囊的预测结果一致，而接受依非韦伦口服溶液治疗的儿童中，依非韦伦浓度低于预期，需要在计划评估点之后增加剂量。
在这项为期两年的研究中，恩曲他滨、去羟肌苷和依非韦伦每日一次给药方案被证明是安全且耐受性良好的，并显示出良好的免疫和病毒学疗效。
