Related Experiment Video
Updated: Aug 9, 2026

A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Hepatitis C virus protease gene diversity in patients coinfected with human immunodeficiency virus
Mark A Winters1, Seth L Welles, Mark Holodniy
1Division of Infectious Diseases and Geographic Medicine, Stanford University, California, USA.
Insights
Hepatitis C virus (HCV) protease gene variability was assessed in HIV-coinfected individuals. Significant within-patient genetic diversity was found, potentially impacting HCV protease inhibitor efficacy.
Area of Science:
- Virology
- Molecular Biology
- Infectious Diseases
Background:
- Hepatitis C virus (HCV) infection is a global health concern.
- Coinfection with human immunodeficiency virus (HIV) complicates HCV management.
- HCV protease inhibitors are crucial for treatment, but viral evolution can lead to resistance.
Purpose of the Study:
- To evaluate the clonal variability of the HCV protease gene in individuals coinfected with HIV.
- To determine if variability differs across HCV genotypes (1a, 1b, 2b, 3a).
- To assess the implications of this variability for HCV protease inhibitor effectiveness.
Main Methods:
- Analysis of HCV protease gene sequences from 24 HIV-coinfected patients.
- Quantification of nucleotide and amino acid variability within and among patients.
- Mixed-model analysis to compare variability across genotypes after adjusting for intrapatient variation.
Main Results:
- Within-genotype nucleotide and amino acid variability ranged from 6.5–8.6% and 2.2–3.8%, respectively.
- Significant intrapatient clonal variability was observed, up to 5.3% at the nucleotide and 5.8% at the amino acid level.
- HCV genotype 1a exhibited significantly greater nucleotide variability compared to other genotypes (P = 0.01).
Conclusions:
- Substantial clonal variability exists within the HCV protease gene at the patient level.
- This intrapatient variability may influence the efficacy of HCV protease inhibitor therapies.
- Further research is needed to understand the clinical impact of HCV genetic diversity in coinfected populations.
Abstract:
The clonal variability of the hepatitis C virus (HCV) protease gene in 24 individuals with HCV genotypes 1a, 1b, 2b, and 3a who were coinfected with the human immunodeficiency virus was evaluated. Within-genotype variability at the nucleotide and amino acid levels ranged from 6.5 to 8.6% and 2.2 to 3.8%, respectively. After adjustments were made for correlation of intrapatient clonal variation, mixed-model analysis indicated that nucleotide and amino acid variability among patients with different genotypes did not differ significantly. However, within individual patients, clonal variability differed by up to 5.3% and 5.8% at the nucleotide and amino acid levels, respectively, and genotype 1a had significantly greater nucleotide variability than other genotypes (P = 0.01). Significant variability exists within HCV protease gene variants at the patient level and could affect the effectiveness of HCV protease inhibitors.
Related Concept Videos
Inhibitors of Virion Maturation and Assembly
Hepatitis
Retrovirus Life Cycles
Viral Mutations
Retroviruses
Viral Hepatitis I: Introduction

