Injection drug abuse is among the several methods of HCV infection. However, until now, current or recent injection drug addicts with HCV were excluded from clinical trials, and largely assumed to be untreatable for the virus. This allowed a sizable proportion of those with HCV (who could potential infect others, including non-drug abusers), to remain infected and at large in the population. A new study published in the American College of Physicians, Annals of Internal Medicine this month, concluded that this previously under-studied population may, in fact, have the possibility to be treated.
Dr. Gregory J. Dore and colleagues conducted a randomized, placebo-controlled, double-blind study between September 2, 2014 and December 9, 2014, in which they analyzed the combination drug elbasvir/grazoprevir’s effectiveness in reducing the viral load in individuals who were currently in drug abuse treatment programs for opioid addiction. The study included 301 patients with HCV genotypes 1, 4, and 6, where 201 individuals received immediate treatment for 12 weeks, and the other 100 received a placebo for 12 weeks, followed by 4 weeks of no treatment, and finally, 12 weeks of open-label treatment with elbasivr/grazoprevir. The combination drug, manufactured by Merck, was originally approved by the FDA for HCV genotypes 1 and 4, however, 5 patients with genotype 6 were included in this study.
The individuals were taking either methadone or buprenorphrine to help control their opioid addiction, with many still using drugs during the study. The researchers concluded that current drug use had no significant effect on the results of the study, which included a primary efficacy endpoint of reducing viral load response to less than 15 IU/mL (the lower limit of quantitation) in 12 weeks. 91.5% of individuals in the immediate treatment group met this efficacy endpoint, as well as 89.5% of individuals in the control group during the active phase of their treatment.
Only 17 individuals did not achieve the desired viral response load after 12 weeks of active treatment, with 12 individuals getting re-infected with HCV, and 5 discontinuing the trial due to administrative reasons or adverse effects of treatment. The only adverse effects of the treatment reported by those who completed the study were nausea, headache, and fatigue. The researchers also included a modified analysis, in which they included patients who were re-infected with HCV as successes of the treatment (meaning that they were cured using the medication, however, were reintroduced to the virus on their own accord). This analysis raised the achieved endpoint level to 94%.
The trial population included roughly 20% of individuals with cirrhosis, as well as 7% of individuals with an HIV co-infection. Results remained fairly consistent for individuals across genotypes 1a, 1b, and 4, however, for the 5 individuals with genotype 6, achievement rates were lowered (20%). This could be due to ethnicity (most with GT 6 are of Asian descent), a small sample size causing bias, or potentially due to the medications primary target population being only genotypes 1 and 4.
Treatment adherence in the trial was around 95%, which is similar to that of the general population. This value, along with the promising results, indicates that the conversation around HCV treatment needs to be modified to include those who are current drug abusers, specifically, those who are seeking or already enrolled in treatment programs. This could allow a much larger population with HCV to be treated for the virus, potentially reducing overall contraction and transmission rates significantly.1-2
Dore GJ et al. Elbasvir-Grazoprevir to treat hepatitis C virus infection in persons receiving opiod agonist therapy: A randomized trial. Annals of Internal Medicine. 9 Aug 2016. Available from: http://annals.org/article.aspx?articleid=2542526.
FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4. U.S. Food and Drug Administration. 28 Jan 2016. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm.