HCV genotype 1b cured with 3-wk triple-drug regimen in Asian population

Last Updated: 2015-11-18

By Megan Brooks

NEW YORK (Reuters Health) - In a small pilot study, Asian patients with hepatitis C virus (HCV) genotype 1b were successfully treated in as few as three weeks with a triple combination of direct-acting antiviral agents.

"We took the three best, most powerful drugs - without regard to manufacturer - and hit the virus with a sledgehammer. And we showed that for some patients, it's possible to stop treatment after just three weeks, which many thought was impossible," Dr. Raymond Schinazi, of Emory University School of Medicine and the Atlanta VA Medical Center (VAMC), who worked on the study, said in a news release.

The study, known as SODAPI, was conducted in Hong Kong in 26 non-cirrhotic patients with chronic HCV genotype 1b, the most common genotype in Asia.

The patients were divided into three treatment groups. Group 1 received sofosbuvir, ledipasvir and asunaprevir (12 patients). Group 2 received sofosbuvir, daclatasvir and simeprevir (six patients). Group 3 received sofosbuvir, daclatasvir and asunaprevir (eight patients).

"We postulated that the addition of an NS3 protease inhibitor to dual NS5A-NS5B (nucleoside) inhibitors would enhance antiviral efficacy and reduce treatment duration to three weeks in individuals with a rapid virologic response (RVR) defined as plasma HCV RNA<500 IU/mL by day two," the study team notes in an abstract presented at the American Association for the Study of Liver Disease (AASLD) meeting in San Francisco this week.

Patients' average viral load before treatment was 3.5 million IU/mL. According to the researchers, a total of 18 patients achieved RVR, including six of 12 patients in group 1, six of six in group 2, and six of eight in group 3.

Using "response-guided therapy," the 18 patients who achieved a RVR continued on their assigned regimen for a total of three weeks. All 18 with RVR had a sustained virologic response (SVR), defined as plasma viral RNA below the limit of detection after 12 weeks, and continue to be monitored.

"To be frank, I was surprised by the findings because everyone has pretty much set their minds that it's not possible to go below six weeks of treatment. This study shows that it can be done in three weeks," Dr. Schinazi noted in an interview with Reuters Health. "For China, I think this could be fantastic because at least 20% of the population is genotype 1b and today it's one of the easiest to treat, sort of the low-hanging fruit."

The patients in the study who didn't achieve a RVR continued treatment with the sofosbuvir/ledipasvir combination for 12 weeks (the current standard of care), and all achieved SVR as well.

"This was a proof of principle study," Dr. Schinazi said in a statement. "The next step is to test the same approach on patients with other genotypes and also in more difficult to treat patient groups. Following the concept of response-guided therapy could usher in an era of ultra-short treatment courses for hepatitis C virus. Ideally, it would be great if drug companies work together to find the best and shortest cure combinations."

Dr. Raymond T. Chung, director of hepatology at Massachusetts General Hospital in Boston, who wasn't involved in the study, urged caution in interpreting the findings.

"This is a study in a limited number of young Asian patients with genotype 1b. With all the experience thus far amassed, genotype 1b infection has proven to be a much more vulnerable subtype of genotype 1 to treat. It's had consistently better rates of response to regimens virtually across the board compared to genotype 1a. It's unlikely we would see this kind of success, at least this rate and with this duration, with genotype 1a," Dr. Chung explained.

"The other aspect of this is that Asian patients have a very high frequency of favorable genetic polymorphisms, which likely contributes to success when one pushes the envelope in terms of treatment duration, which was done in this study," he noted. The findings are "exciting but not widely generalizable."

Dr. Chung said, "It's also important to remember that we are achieving nearly 100% success using more conventional durations and not necessarily even using triple regimens. So the question is, when do you need to soup it up with a three-drug regimen and how important is it to shorten the duration for some compared to having a terrific outcome for just about all using a longer duration and fewer drugs. The question comes down to whether it's practical."

Dr. Schinazi has an equity interest in the manufacturers of two of the drugs in the study. No other disclosures were reported.