Baseline Viral Load Suboptimal in Predicting Elbasvir/Grazoprevir Efficacy
The presence of NS5A RASs at baseline appears to represent a more robust method for identifying individuals with HCV genotype 1a infection.
Baseline testing for nonstructural protein 5A (NS5A) resistance-associated substitutions enables more patients to receive 12 weeks of elbasvir/grazoprevir therapy without compromising the opportunity for sustained virologic response when compared with using baseline viral load as a stratification factor to define antiviral regimens, according to a study published in the Journal of Viral Hepatitis.
Although European treatment guidelines recommend that patients with hepatitis C (HCV) genotype 1a who have a baseline viral load of ≤800,000 IU/mL receive elbasvir/grazoprevir for 12 weeks, and those with a baseline viral load of >800,000 IU/mL receive elbasvir/grazoprevir plus ribavirin for 16 weeks, current treatment guidelines in the United States recommend testing for baseline NS5A resistance-associated substitutions first, as these variants are associated with elbasvir resistance.
Researchers conducted this post hoc analysis on data from participants with HCV gentotype 1a infection from 11 clinical trials of elbasvir/grazoprevir to determine if baseline viral load is a sufficiently sensitive, accurate, or specific stratification factor to define medication regimens. Trial participants had to receive 12 weeks of elbasvir 50 mg/grazoprevir 100 mg to be eligible for analysis, and the primary end point was sustained virologic response 12 weeks post treatment.
In total, 911 of the 957 (95.2%) participants included in the study achieved the primary end point of sustained virologic response 12 weeks after the treatment, and this rate was higher in participants with baseline viral loads of ≤800,000 IU/mL compared with those with baseline viral loads of >800,000 IU/mL (98.5% vs 93.9%). Using 800,000 IU/mL as a threshold yielded an overall accuracy of 31.5%, a negative predictive value of 6.1%, a positive predictive value of 98.5%, a sensitivity of 28.4%, and a specificity of 91.3%.
Baseline NS5A resistance-associated substitutions were detectable in 25% of virologic failures in participants with baseline viral loads of ≤800,000 IU/mL, compared with 59.5% of participants with baseline viral loads of >800,000 IU/mL, regardless of sex, treatment history, body mass index, HIV coinfection, or presence of cirrhosis.
Study investigators concluded that “a baseline viral load cutpoint of 800,000 IU/mL had high positive predictive value and specificity, but poor negative predictive value, sensitivity, and accuracy in predicting treatment outcomes…baseline testing for NS5A [resistance-associated substitutions] enables more individuals to receive the 12-week [elbasvir/grazoprevir] regimen without compromising the opportunity for [sustained virologic response]."
Study funding was provided by Merck & Co., Inc.
Serfaty L, Jacobson I, Rockstroh J, et al. The accuracy of baseline viral load for predicting the efficacy of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1a infection: an integrated analysis [published online November 9, 2018]. J Viral Hepat. doi: 10.1111/jvh.13037