Sofosbuvir, a New Nucleotide Analogue, for the Treatment of Chronic Hepatitis C Infection

Objective: To evaluate the clinical role of sofosbuvir (Solvadi) in the treatment of hepatitis C virus (HCV). Data Sources: A MEDLINE, EMBASE, and Cochrane search indexed from January 2000 to July 2014 was performed using the search terms GS-7977 and sofosbuvir. Study Selection and Data Extraction: Studies including humans subjects, published in English, and assessing efficacy and safety of sofosbuvir in management of chronic HCV were evaluated. Data Synthesis: 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. Conclusions: 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.