TreatmentUpdate
213

February 2016 

Zepatier in people grappling with drug addiction

In Canada and other high-income countries the main way that HCV infection generally spreads today is through sharing equipment for substance use.

Researchers in Canada, Australia, Europe, Israel, Taiwan and the U.S. collaborated in a study called Co-Star that sought to treat HCV in people who use street drugs.

Co-Star was a placebo-controlled trial wherein 301 participants were randomly assigned to receive either Zepatier or fake Zepatier (placebo) for 12 consecutive weeks. After the end of this period, participants who had received placebo were offered treatment with Zepatier.

For at least three months prior to entering the study, participants would have been receiving care and treatment for addiction and taking therapies associated with addiction treatment, including the following:

  • buprenorphine (Suboxone)
  • methadone
  • naloxone
  • naltrexone

In that time period, participants were supposed to have kept 80% of their scheduled drug treatment appointments.

The average profile of participants at the start of the study was as follows:

  • age – 48 years
  • 76% men, 24% women
  • most (55%) participants had an HCV viral load greater than 2 million IU/mL
  • common genotypes of HCV were: GT1a (76%); GT1b (15%); GT4 (6%) and GT6 (3%)
  • 21% of participants had extensive scarring of the liver (cirrhosis)
  • 7% of participants were co-infected with HCV and HIV
  • among those taking potent combination anti-HIV therapy (ART), commonly used drugs included raltegravir (Isentress), dolutegravir (Tivicay and in Triumeq) and rilpivirine (Edurant and in Complera)

On the first day of the study, urine testing for opiates revealed that 58% of participants were still using street drugs.

Results

In an analysis that excluded participants who left the study for reasons unrelated to treatment, 96% of participants were cured. Rates of cure were not generally different among the different genotypes of HCV, with one exception: Only three of five participants with genotype 6 infection were cured in this study. It is important to note that regulatory authorities have not approved Zepatier for the treatment of genotype 6 infection.

There were seven cases of relapse.

Five other participants were initially cured of HCV but subsequently developed elevated HCV viral loads. Technicians testing blood samples from these five found that they had been re-infected with a different strain of HCV.

Screening for street drugs

Participants had their urine screened for the presence of the following classes of street drugs:

  • amphetamines
  • barbiturates
  • benzodiazepines
  • cannabinoids
  • cocaine
  • opiates
  • phencyclidine
  • propoxyphene

Substance use was steady during the study, with about 60% of participants testing positive for the above-mentioned classes of drugs.

According to the researchers, adherence to the study medications was high, averaging between 97% and 100%. Researchers did not provide details as to how adherence was assessed.

Adverse events

Common side effects were distributed as follows:

Unexpected tiredness or lack of energy

  • Zepatier – 16%
  • placebo – 20%

Headache

  • Zepatier – 13%
  • placebo – 14%

Nausea

  • Zepatier – 11%
  • placebo – 9%

Diarrhea

  • Zepatier – 10%
  • placebo – 9%

Two people taking Zepatier and another taking placebo left the study prematurely because of perceived side effects.

One person who received placebo died from an undisclosed cause.

Key points

Zepatier was highly effective in participants who were taking opioid substitution therapy. Zepatier was generally safe. Substance use was stable throughout the study and adherence was good. The Co-Star study was important because it showed that HCV-positive people who use street drugs and who are being treated for addiction can successfully take modern anti-HCV treatment and be cured.

—Sean R. Hosein

REFERENCE:

Dore GJ, Altice F, Litwin AH. Co-Star—efficacy of grazoprevir and elbasvir fixed-dose combination for 12 weeks in HCV-infected persons who inject drugs on opioid agonist therapy. American Association for the Study of the Liver Disease, 13-17 November 2015. Abstract 40.