Larru Beatriz, Eby Jessica, Lowenthal Elizabeth D
Department of Pediatrics, Division of infectious Diseases, Children's Hospital of Philadelphia, Philadelphia.
Department of Pediatrics, Division of General Pediatrics, Children's Hospital of Philadelphia, Philadelphia ; Villanova University, Villanova.
Pediatric Health Med Ther. 2014 May 29;5:29-42. doi: 10.2147/PHMT.S47794.
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), used for the treatment of human immunodeficiency virus (HIV)-1 infection. Approved by the US Food and Drug Administration in 1998, its indication was recently extended to include children as young as 3 months of age. The World Health Organization and many national guidelines consider efavirenz to be the preferred NNRTI for first-line treatment of children over the age of 3 years. Clinical outcomes of patients on three-drug antiretroviral regimens which include efavirenz are as good as or better than those for patients on all other currently approved HIV medications. Efavirenz is dosed once daily and has pediatric-friendly formulations. It is usually well tolerated, with central nervous system side effects being of greatest concern. Efavirenz increases the risk of neural tube defects in nonhuman primates and therefore its use during the first trimester of pregnancy is limited in some settings. With minimal interactions with antituberculous drugs, efavirenz is preferred for use among patients with HIV/tuberculosis coinfection. Efavirenz can be rendered inactive by a single point mutation in the reverse transcriptase enzyme. Newer NNRTI drugs such as etravirine, not yet approved for use in children under the age of 6 years, may maintain their activity following development of efavirenz resistance. This review highlights key points from the existing literature regarding the use of efavirenz in children and suggests directions for future investigation.
依非韦伦是一种非核苷类逆转录酶抑制剂(NNRTI),用于治疗人类免疫缺陷病毒1型(HIV-1)感染。1998年获美国食品药品监督管理局批准,其适应证最近扩大到包括3个月大的儿童。世界卫生组织和许多国家指南认为依非韦伦是3岁以上儿童一线治疗的首选NNRTI。包含依非韦伦的三联抗逆转录病毒治疗方案的患者临床结局与目前所有其他获批的HIV药物治疗的患者一样好或更好。依非韦伦每日给药一次,有适合儿童的剂型。它通常耐受性良好,最值得关注的是中枢神经系统副作用。依非韦伦会增加非人灵长类动物神经管缺陷的风险,因此在某些情况下,孕期头三个月使用它受到限制。由于与抗结核药物的相互作用最小,依非韦伦是HIV/结核合并感染患者的首选用药。逆转录酶的单点突变可使依非韦伦失活。较新的NNRTI药物,如依曲韦林,尚未获批用于6岁以下儿童,在依非韦伦耐药发生后可能仍保持活性。本综述强调了现有文献中关于依非韦伦在儿童中使用的关键点,并提出了未来研究的方向。