Treatment intensification with sofosbuvir permits cure after failure of previous HCV treatment

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Re-treating with an interferon-free regimen that previously failed to cure hepatitis C can result in success if treatment is intensified with the addition of sofosbuvir, two studies presented at the 2015 AASLD Liver Meeting have shown.

Although direct-acting antiviral treatment results in cure rates above 90% in most groups of patients with hepatitis C genotypes 1 and 2, including people with cirrhosis, a small proportion of people experience viral relapse. For those with advanced liver disease it may not be possible to wait until new drugs become available, and other options are needed.

One concern is that failure of a regimen that contains an NS5A inhibitor (ledipasvir in Harvoni, ombitasvir in Viekira Pak / Viekira) may result in the emergence of NS5A-resistant virus that can take up to 96 weeks to disappear. NS5A inhibitors may have some activity against these variants, but further treatment with an NS5A inhibitor could result in higher-level resistance if hepatitis C is not rapidly suppressed. Adding an agent of a new class could increase antiviral activity.



Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 


The return of signs and symptoms of a disease after a patient has been free of those signs and symptoms. 


A drug that acts against a virus or viruses.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

Two companies presented data at the Liver Meeting showing successful re-treatment when sofosbuvir was added to the regimen used previously, or people were re-treated with a new regimen to which they might have some resistance. Merck reported findings from a study of treatment intensification in people who failed a short course of treatment lasting less than eight weeks with its investigational protease inhibitor/NS5A inhibitor combination, and AbbVie reported findings from a study of treatment intensification in people who failed treatment with ombitasvir, paritaprevir/r and dasabuvir (Viekira Pak / Viekirax & Exviera)(paritaprevir levels are boosted by ritonavir).

Merck: C-SWIFT re-treatment study

Merck’s C-SWIFT re-treatment study looked at the effect of adding sofosbuvir and ribavirin to elbasvir (NS5A inhibitor) and grazoprevir (protease inhibitor) in people with genotype 1 infection who had experienced virologic relapse after treatment with elbasvir and grazoprevir given for four, six or eight weeks. Twenty-five people who had experienced relapse in the cirrhotic and non-cirrhotic arms of the C-SWIFT study were enrolled, a median of 214 days after virologic failure in the C-SWIFT study.

Participants were predominantly male (88%) with a mean age of 54 years. 88% had genotype 1a infection, and 20% had cirrhosis. 80% had baseline NS5A resistance mutations, 52% had baseline NS3 protease mutations, and 44% had some resistance to both drug classes. None had resistance mutations in the NS5B polymerase region targeted by sofosbuvir.

Treatment was given for 12 weeks, and 12 weeks after the completion of treatment all participants had a sustained virologic response. Two participants were lost to follow-up at day 3 and week 4.

Overall, treatment was well tolerated with only one serious adverse event. Two people discontinued ribavirin due to pruritus and anaemia respectively, but went on to achieve SVR12.

AbbVie: QUARTZ-1 study

AbbVie’s QUARTZ-1 study examined the impact of adding sofosbuvir and ribavirin, or sofosbuvir alone, to its Viekira Pak / Viekira & Exviera regimen. The open-label study recruited 22 participants who had experienced viral failure or relapse after first-line treatment with a variety of regimens, not restricted to AbbVie’s own combination. Participants were assigned as follows:

  • Genotype 1a, no cirrhosis (n = 14): 12 weeks of treatment with ombitasvir, paritaprevir/r and dasabuvir, plus sofosbuvir and ribavirin.
  • Genotype 1a, cirrhosis (n = 6): 24 weeks of treatment with ombitasvir, paritaprevir/r and dasabuvir, plus sofosbuvir and ribavirin.
  • Genotype 1b, with or without cirrhosis (n=2): 12 weeks of treatment with ombitasvir, paritaprevir/r and dasabuvir, plus sofosbuvir.

Paritaprevir levels are boosted by ritonavir.

All participants with genotype 1a and cirrhosis had been treated previously with ombitasvir, paritaprevir/r and dasabuvir. Ten out of 14 genotype 1a participants without cirrhosis had received ombitasvir, paritaprevir/r and dasabuvir (8) or ombitasvir and paritaprevir/r (2). Four of the remaining six had received an HCV protease inhibitor in combination with either sofosbuvir or an experimental agent

Those receiving treatment for 12 weeks had the option of continuing treatment for a further 12 weeks if HCV was still detectable at week 12. In the event one participant with genotype 1a infection received extended treatment.

Twelve weeks after the completion of treatment 14 of 15 participants who had received 12 weeks of treatment had a sustained virological response (SVR12). One participant experienced virological relapse; this patient had no evidence of baseline resistance.

In those who received 24 weeks of treatment post-treatment virologic data to week 4 (SVR4) show no cases of virological relapse.

Over half of participants had at least one mutation associated with resistance to NS3 protease inhibitors, and over half had at least one mutation associated with resistance to NS5A inhibitors.

The single virological failure occurred in a participant previously treated with telaprevir (a first-generation HCV protease inhibitor), pegylated interferon and ribavirin.


Lawitz E et al. C-SWIFT Retreatment (Part B): 12 weeks of elbasvir/grazoprevir with sofosbuvir and ribavirin successfully treated GT1-infected subjects who failed short-duration all-oral therapy. AASLD Liver Meeting, San Francisco, abstract LB-12, 2015.

Poordad F et al. QUARTZ-1: Re-treatment of HCV genotype 1 DAA failures with ombitasvir, paritaprevir/r, dasabuvir and sofosbuvir. AASLD Liver Meeting, San Francisco, abstract LB-20, 2015.