Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa A Randomized Clinical Trial
Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa A Randomized Clinical Trial
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DOI：
10.1001/jama.2015.13631
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发表时间：
2015-11-03
影响因子：
120.7
通讯作者：
Kuhn, Louise
中科院分区：
文献类型：
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作者：
Coovadia, Ashraf;Abrams, Elaine J.;Kuhn, Louise
使用依非韦伦作为治疗感染人类免疫缺陷病毒（HIV）的儿童的一部分的优点包括每日一次给药，简化结核病的联合治疗，保留利托那韦增强的洛匹那韦用于二线治疗，以及成人和儿童治疗方案的统一。然而，对于暴露于奈韦拉平预防母婴传播的儿童，有可能降低依非韦伦的病毒功效。目的评估暴露于奈韦拉平的儿童在接受利托那韦增强的洛匹那韦为基础的治疗获得初始病毒抑制后，是否可以过渡到以依非韦伦为基础的治疗而没有病毒衰竭的风险。设计、环境和参与者：2010年6月至2013年12月，在南非约翰内斯堡的Rahima Moosa妇幼医院进行了一项随机、开放标签的非劣效性试验，招募了300名接受奈韦拉平治疗以预防母婴传播的3岁或以上的艾滋病毒感染儿童，这些儿童在利托那韦增强洛匹那韦治疗期间血浆HIV RNA低于50拷贝/mL；298例随机化，292例（98%）随访至随机化后48周。干预措施参与者被随机分配到以依非韦伦为基础的治疗（n = 150）或继续以利托那韦增强的洛匹那韦为基础的治疗（n = 148）。两组间在(1)病毒反弹（即>= 1 HIV RNA测量>50拷贝/mL）和(2)病毒衰竭（即确认HIV RNA >1000拷贝/mL）方面的风险差异，非效性界限为-0.10。免疫和临床反应是次要终点。结果依非韦伦组48周病毒反弹Kaplan-Meier概率为0.176 (n = 26)，利托那韦增强洛匹那韦组48周病毒反弹Kaplan-Meier概率为0.284 （n = 42）。依非韦伦组病毒失败的概率为0.027 (n = 4)，利托那韦增强洛匹那韦组为0.020 （n = 3）。病毒反弹的风险差异为0.107（单侧95% CI， 0.028至无穷大），病毒失败的风险差异为-0.007（单侧95% CI， -0.036至无穷大）。在两个终点，我们拒绝了依非韦伦次于利托那韦的洛匹那韦的原假设（P < 0.001）。48周时，依非韦伦组CD4细胞百分比比利托那韦增强洛匹那韦组高2.88%（95% CI, 1.26%-4.49%）。在暴露于奈韦拉平预防母婴传播的hiv感染儿童中，最初使用利托那韦增强的洛匹那韦为基础的治疗来抑制病毒，与继续使用利托那韦增强的洛匹那韦为基础的治疗相比，改用依非韦伦为基础的治疗不会导致病毒反弹或病毒衰竭的显着增加。这种治疗方法可能对这些儿童有好处。
IMPORTANCE Advantages of using efavirenz as part of treatment for children infected with human immunodeficiency virus (HIV) include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission.OBJECTIVE To evaluate whether nevirapine-exposed children achieving initial viral suppression with ritonavir-boosted lopinavir-based therapy can transition to efavirenz-based therapy without risk of viral failure.DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label noninferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, from June 2010 to December 2013, enrolling 300 HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission who were aged 3 years or older and had plasma HIV RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy; 298 were randomized and 292 (98%) were followed up to 48 weeks after randomization.INTERVENTIONS Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148).MAIN OUTCOMES AND MEASURES Risk difference between groups in (1) viral rebound (ie, >= 1 HIV RNA measurement of >50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000 copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical responses were secondary end points.RESULTS The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and 0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to infinity) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to infinity). We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. By 48 weeks, CD4 cell percentage was 2.88%(95% CI, 1.26%-4.49%) higher in the efavirenz group than in the ritonavir-boosted lopinavir group.CONCLUSIONS AND RELEVANCE Among HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission and with initial viral suppression with ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these.