Some interferon-free regimens have demonstrated efficacy for genotypes 4 and 6, but these may not be widely available because of cost or other issues. Other regimens for genotypes 4, 5, and 6 continue to include peginterferon and
ribavirin. The decision to treat a patient at this time or await availability of interferon-free regimens should take into account the expected efficacy and adverse effects of available regimens, history of prior antiviral therapy, the current liver disease stage, extrahepatic manifestations, and patient preference. (See
'Deciding when to treat' above.)
●Effective interferon-free regimens for genotype 4 infection include
ledipasvir-sofosbuvir for 12 weeks, ombitasvir-paritaprevir-ritonavir plus weight-based
ribavirin for 12 weeks, and
sofosbuvir plus weight-based ribavirin for 24 weeks. The choice between them depends primarily on potential for drug interactions, availability, and cost. If these are not issues, we suggest ledipasvir-sofosbuvir (
Grade 2C). If interferon-free regimens are not available, 12 weeks of sofosbuvir plus peginterferon and weight-based ribavirin is also highly effective for treatment-naïve patients but has the added toxicity of peginterferon. Furthermore, the efficacy of this regimen is uncertain in treatment-experienced patients. (See
'Genotype 4' above.)
●Data on treatment of genotype 5 infection are extremely limited. For patients with genotype 5 infection who are initiating treatment now, we suggest
sofosbuvir plus peginterferon and weight-based
ribavirin for 12 weeks (
Grade 2C). For patients who do not have access to sofosbuvir, the alternative regimen is 48 weeks of peginterferon and ribavirin. (See
'Genotype 5' above.)
●Data on treatment of genotype 6 infection is limited. For patients with genotype 6 infection who are initiating treatment now, we suggest
ledipasvir-sofosbuvir for 12 weeks (
Grade 2C). If this interferon-free regimen is cost-prohibitive or otherwise unavailable, the 12 week regimen of
sofosbuvir plus peginterferon and weight-based
ribavirin is also expected to be highly effective in the treatment-naïve. (See
'Genotype 6' above.)
●Interferon-free regimens are generally well tolerated, although the potential for drug interactions should be reviewed.
Ribavirin is potentially teratogenic, so two effective forms of contraception should be used by both men and women of child-conceiving potential during and six months after treatment with ribavirin-containing regimens. Peginterferon and ribavirin are associated with a number of other side effects. These issues are discussed in detail elsewhere. (See
"Direct-acting antivirals for the treatment of hepatitis C virus infection" and
"Management of the side effects of peginterferon and ribavirin used for treatment of chronic hepatitis C virus infection".)
