Yancey Abigail, Armbruster Anastasia, Tackett Stephanie
St Louis College of Pharmacy, St Louis, MO, USA.
J Pharm Technol. 2015 Feb;31(1):29-37. doi: 10.1177/8755122514548897. Epub 2014 Sep 4.
To evaluate the clinical role of sofosbuvir (Solvadi) in the treatment of hepatitis C virus (HCV). A MEDLINE, EMBASE, and Cochrane search indexed from January 2000 to July 2014 was performed using the search terms GS-7977 and sofosbuvir. Studies including humans subjects, published in English, and assessing efficacy and safety of sofosbuvir in management of chronic HCV were evaluated. Sofosbuvir, a nucleotide analogue NS5B polymerase inhibitor, competes with nucleotides within the hepatocytes resulting in chain termination and inhibition of RNA replication. Trials evaluating the efficacy of sofosbuvir combination therapy have demonstrated significant advantage in sustained virologic response (SVR) over previous therapies. Genotype 1, 4, 5, and 6 patients treated with peginterferon-α, ribavirin, and sofosbuvir for 12 weeks achieved SVR rates of 90%. Twelve-week peginterferon-free regimens have resulted in SVR rates of 90% in genotype 2 patients, whereas genotype 3 patients required 24 weeks of therapy to achieve similar results. Favorable SVR rates were also seen in previously difficult-to-treat patient populations including cirrhosis, HIV coinfection, and treatment-experienced. Sofosbuvir appears to be well tolerated and relatively safe, avoiding severe adverse drug reactions, laboratory abnormalities, and resistance issues associated with traditional HCV therapies. The biggest limitation of sofosbuvir is the high cost associated with therapy. Sofosbuvir is a safe and effective treatment option for patients infected with genotypes 1 to 6 HCV including previously difficult-to-treat populations. The shorter duration, oral route, minimal side effects, and decreased resistance potential makes it a welcome addition to the treatment of chronic HCV.
评估索非布韦（索华迪）在丙型肝炎病毒（HCV）治疗中的临床作用。使用检索词GS - 7977和索非布韦对2000年1月至2014年7月期间的MEDLINE、EMBASE和Cochrane数据库进行检索。评估纳入人类受试者、以英文发表、评估索非布韦治疗慢性HCV的疗效和安全性的研究。索非布韦是一种核苷酸类似物NS5B聚合酶抑制剂，与肝细胞内的核苷酸竞争，导致链终止并抑制RNA复制。评估索非布韦联合治疗疗效的试验表明，与先前的治疗相比，在持续病毒学应答（SVR）方面具有显著优势。接受聚乙二醇干扰素-α、利巴韦林和索非布韦治疗12周的1、4、5和6型患者的SVR率达到90%。对于2型患者，12周无聚乙二醇干扰素方案的SVR率达到90%，而3型患者需要24周治疗才能取得类似结果。在先前难以治疗的患者群体中，包括肝硬化、合并HIV感染和有治疗经验的患者，也观察到了良好的SVR率。索非布韦似乎耐受性良好且相对安全，避免了与传统HCV治疗相关的严重药物不良反应、实验室异常和耐药问题。索非布韦最大的局限性是治疗费用高昂。索非布韦是治疗感染1至6型HCV患者（包括先前难以治疗的人群）的一种安全有效的治疗选择。疗程较短、口服给药、副作用最小以及耐药可能性降低，使其成为慢性HCV治疗中受欢迎的补充药物。
