New and Noteworthy
In this issue of HepCinfo Update, we cover selected results from four clinical trials of Hep C medication combinations presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014).
These trials are noteworthy for a number of reasons:
- The cure rates in all of these trials are very high (85-99%).
- They are all trials of combinations of two or three direct-acting anti-virals that do not include interferon and in some cases do not include ribavirin. Both interferon and ribavirin can cause significant side effects.
- The treatment lengths being tested are all 12 weeks, which is much shorter than most currently available treatments.
- Two of the trials involve participants who do not do well on standard interferon-based treatments but did have high cure rates with these new medications. These groups were people with genotype 1a virus and people co-infected with Hep C and HIV.
Treatment with three direct-acting anti-virals cures 99% of people with genotype 1b Hep C virus
A 12-week treatment with a combination of three direct-acting anti-virals cured 99% of people with genotype 1b virus, reported researchers at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) in Boston.
In this late-stage trial of 419 people, participants received a combination of three direct-acting anti-virals (ABT-450, ABT-267, ABT-333) with or without ribavirin. The cure rates were similar in the trial arms with and without ribavirin (99.5% and 99%).
The majority of participants had little or no liver damage. Participants had either never been treated for Hep C before or had previously gone through treatment.
The treatment was well tolerated with only approximately 1 in 5 participants experiencing side effects. Side effects included headache and fatigue. Some people experienced anemia in the trial arm that included ribavirin.
The researchers concluded that this combination, also known as 3D, could be delivered without ribavirin for people with genotype 1b virus. (HIVandhepatitis.com, March 2014, in English)
A combination of three direct-acting anti-virals cures over 90% of people with genotype 1a virus
Over 90% of participants in a 12-week trial of daclatasvir, asunaprevir and BMS-791325 were cured of hepatitis C, reported researchers at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) in Boston. The majority of participants had never been treated before. Most participants had the harder-to-treat genotype 1a virus and almost 40% had advanced liver damage.
166 participants were randomly assigned to receive daclatasvir, asunaprevir and either 75mg or 150mg of BMS-791325.
The cure rate for participants with genotype 1a virus was 91% in both treatment arms. For people with genotype 1b virus the cure rate was 100% (combination with 75 mg of BMS-791325) and 94% (combination with 150mg of BMS-791325).
This treatment combination was well tolerated. The most common side-effects were headache, diarrhea, fatigue and nausea.
“This 12-week, interferon- and ribavirin-free, all-oral 3-DAA regimen achieved SVR12 in >90% of patients despite high prevalence of genotype 1a, advanced fibrosis/cirrhosis, and IL28B non-CC genotypes,” the researchers concluded. (aidsmap.com, March 2014, in English)
Daclatasvir and simeprevir effective against genotype 1b virus, not genotype 1a
Daclatasvir plus simeprevir, without interferon or ribavirin, led to a cure rate of 85 to 95% in people with hepatitis C genotype 1b, but this combination did not work well against genotype 1a virus, reported researchers at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
147 participants with genotype 1b virus received daclatasvir and simeprevir with or without ribavirin for 12 weeks. After 12 weeks they were randomized to either stop treatment or continue for another 12 weeks. 21 participants with genotype 1a received daclatasvir, simeprevir and ribavirin for 24 weeks.
Just over one third of the participants had advanced liver damage. Just under one third had previously been treated but did not respond to treatment (null responders), while the rest of the participants had never been treated (treatment naïve).
Cure rates for participants with genotype 1b virus who were treatment naïve:
- Daclatasvir and simeprevir: 85% SVR
- Daclatasvir, simeprevir and ribavirin: 75% SVR
Cure rates for participants with genotype 1b virus who were prior null responders:
- Daclatasvir and simeprevir: 65% SVR
- Daclatasvir, simeprevir and ribavirin: 95% SVR
The cure rates for participants with genotype 1b virus treated with daclatasvir, simeprevir and ribavirin for 12 weeks was similar to those who took the same treatment for 24 weeks.
Participants with genotype 1a virus who had never been treated had a cure rate of 67%, while the majority of prior null responders with the genotype 1a did not clear the virus with the daclatasvir, simeprevir and ribavirin treatment.
According to the researchers, these results suggest that people with genotype 1b could be treated with daclatasvir and simeprevir without ribavirin for 12 weeks. (HIVandhepatitis.com, March 2014, in English)
Two-drug combination may work well for people co-infected with Hep C and HIV
A 12-week combination of two drugs (MK-5172 and MK-8742) without interferon or ribavirin worked well for people co-infected with Hep C and HIV, reported researchers at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
Participants in this mid-stage trial had never been treated before and did not have liver damage. Participants were all on HIV treatment with well controlled HIV.
There were two trial arms with a total of 59 people:
- MK-5172, MK-8742 and ribavirin for 12 weeks
- MK-5172 and MK-8742 for 12 weeks
In the first trial arm, at the end of treatment, 100% of participants had an undetectable viral load. In the second treatment arm 90% had an undetectable viral load at the end of treatment. An end-of- treatment response rate is not considered a cure because people can still relapse after the end of treatment. Having an undetectable viral load 12 weeks after the end of treatment is considered a cure. This is also known as sustained virological response 12 or SVR 12. A previous trial of these medications with people who only had Hep C had similar end-of-treatment response rates.
Both treatments were generally safe and well tolerated. The most common side-effects were fatigue, headache, nausea and diarrhea. A very small group of participants in the ribavirin-containing arm developed anemia.
These results support an emerging trend in studies of Hep C direct-acting antiviral combinations that show that response rates that are equally good and side-effects are no worse for people with HIV and Hep C co-infection compared to those with HCV alone. This is in contrast to interferon treatments, which are both less effective and associated with more serious side effects in people living with HIV.