What is the role of direct-acting antiviral agents (DAAs) in the treatment of hepatitis C (hep C) infection?

Updated: Oct 07, 2019
  • Author: Vinod K Dhawan, MD, FACP, FRCPC, FIDSA; Chief Editor: BS Anand, MD  more...
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Answer

Relatively recently, several antiviral agents have been developed to specifically target various sites of hepatitis C (HCV) viral replication. Similar to the antiretroviral drugs, these agents have been approved by the FDA in various combinations to interrupt HCV replication at different sites, with reported 90%-95% sustained virologic response (SVR) rates in treated patients versus 50%-70% in those completing treatment with dual-therapy pegylated interferon (PEG-IFN) plus ribavirin. [100] However, clinicians should be aware that baseline resistance-associated substitutions (RASs) may impair treatment response to direct-acting antiviral agents (DAAs), particularly baseline NS5A resistance in DAA-naïve HCV patients. [101]

The World Health Organization (WHO) recommends the use of pangenotypic DAA regimens to treat chronic HCV-infected individuals aged 18 years and older. [50] All pangenotypic DAAs (sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/velpatasvir/voxilaprevir) showed similar SVR12 rates. SAEs and DAEs also were comparable between the pangenotypic DAAs and ledipasvir/sofosbuvir. There are very limited data in treatment-naïve patients for the triple DAA combination (sofosbuvir/velpatasvir/voxilaprevir). WHO recommends preserving this regimen for patients who have failed previous DAA treatment (in line with AASLD/IDSA recommendations). [50]

WHO and AASLD/IDSA recommendations for chronic HCV-infected teens aged 12-17 years or weighing at least 35 kg (77.16 lb) are as follows [50] :

  • Genotype 1, 4, 5, and 6: Sofosbuvir/ledipasvir for 12 weeks (treatment naïve without cirrhosis or with compensated cirrhosis; treatment experienced without cirrhosis) or 24 weeks (treatment experienced with compensated cirrhosis)
  • Genotype 2: Sofosbuvir/ribavirin for 12 weeks (treatment naïve or experienced, without cirrhosis or with compensated cirrhosis)
  • Genotype 3: Sofosbuvir/ribavirin for 24 weeks (treatment naïve or experienced, without cirrhosis or with compensated cirrhosis)
  • Genotypes 4, 5, or 6: Sofosbuvir/ledipasvir for 12 weeks (treatment naïve or experienced, without cirrhosis or with compensated cirrhosis)

In chronic HCV-infected children younger than 12 years, the WHO recommends deferring DDA treatment until they are aged 12, as well as to discontinue the use of interferon-based regimens in this population. As physicians await approval and availability of DAAs for children younger than 12 years of age, treatment with IFN plus ribavirin may be considered for those children with genotype 2 or 3 infection, and severe liver disease. This also includes children at higher risk of progressive disease, including those with HIV coinfection, thalassemia major, and childhood cancer survivors. Clinical trial results of DDAs in children aged 6-12 years are starting to emerge. [50]


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