Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response

Abstract

Background & aims: The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure.

Methods: We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12.

Results: The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (≥3.5 g/dL), lower total bilirubin (≤1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use.

Conclusions: Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

Keywords: Antiviral; DAA; NS5A Inhibitor; NS5B Inhibitor.

Figure 1

In the per-protocol population, the SVR12 rate was 96% (95% CI, 95%–97%) among 1788 treated with LDV/SOF and 97% (95% CI, 94%–98%) among 311 treated with LDV/SOF plus RBV. Most of the treatment failures were due to relapse. A total of 7 patients had either virologic breakthrough or failure to achieve unquantifiable HCV RNA on treatment.

Figure 2

Only patients who completed treatment with LDV/SOF and have available virologic outcome included (per-protocol population; n = 1788). LCL and UCL are the lower and upper limits of the 95% confidence interval for the SVR12.

Figure 3

Only patients who completed treatment with LDV/SOF and have available virologic outcome included (per-protocol population; n = 1788). Each entry in Figure 3 represents a different Firth-penalized logistic regression model for SVR conditional on specified covariables. The entry for “male” represents the effect of being male in a logistic regression model for SVR in which “being male” is the only explanatory covariate. Similarly, the entry “age” represents other univariable model. Subsequent entries (eg, “white”) represent models for the probability of SVR as a function of the variable mentioned (eg, being white) with covariate adjustment for “age” and “sex.” HGB, hemoglobin; LCL, lower limits of the 95% confidence interval for the OR; Nobs, number of observations (patients) contributing data to the fitted model; this number varies due to missing values in the baseline covariables; TBIL, total bilirubin; UCL, upper limits of the 95% confidence interval for the OR.