High rates of reinfection in people who inject drugs are a sign that access to treatment is improving, not a sign of failure, and should prompt retreatment, not stigmatisation, Australian hepatitis researcher Greg Dore says in the Journal of Viral Hepatitis this month.
He was commenting on a recently-published study of hepatitis C treatment and HCV reinfection among high-frequency injectors in Dundee, Scotland.
The Eradicate study was designed to evaluate engagement in treatment, cure rates and reinfection rates among active injectors attending needle and syringe programmes in the city. The study defined active injecting as injecting within the previous week, in contrast to other studies in people who use drugs, which required a period of abstinence from injecting prior to treatment or required participants to be receiving opioid substitution treatment.
Everyone attending the main needle and syringe programme in Dundee between January 2012 and July 2016 was tested for hepatitis C antibodies by dried blood spot testing each year. Everyone who tested positive for hepatitis C was offered treatment with pegylated interferon and ribavirin. Anyone who opted for treatment and who had injected in the past week was eligible to join the study.
Of 745 tested for HCV, 92 tested positive for HCV RNA and 69 joined the study, together with 36 people already diagnosed with chronic HCV infection. Ninety-four eventually started treatment. Participants had a median age of 34 years, just over one in five were homeless or living in a hostel and 12% spent time in prison during the treatment period. The median injecting frequency was 6.5 times a week and 54% injected at least once day.
Almost all participants had 100% needle and syringe provision; 82% received needles and syringes sufficient to cover all reported injections and 62.5% were already receiving opioid substitution therapy prior to enrolment.
A high proportion of participants achieved a cure of hepatitis C on pegylated interferon and ribavirin (and a protease inhibitor for genotype 1 infections). 82% achieved a sustained virologic response. 37 patients with genotype 1 infection received simeprevir or telaprevir in addition to pegylated interferon and ribavirin, following NHS guidelines during the study period. There was no difference in cure rate according to genotype.
Adherence to opioid substitution treatment was high during the study; 93.8% of those who began the study on OST remained on OST throughout the study.
Of the 77 participants who achieved a sustained virologic response, five became reinfected with HCV within six months of their 12-week post-treatment follow-up visit, a reinfection rate of 23.53 per 100 person-years of follow-up. After 18 months, 15 of 77 had been reinfected, a cumulative 18-month rate of 21.49/100 person-years. No factors were significantly associated with reinfection in univariate analysis.
Despite the use of older regimens, the study achieved a high cure rate in active drug users. Investigators say that a higher cure rate would be possible with more effective, better tolerated direct-acting antivirals that can be taken for eight or twelve weeks.
The reinfection rate in this study was much higher than reported in a recent meta-analysis of studies (1.77 per 100 person-years) but the investigators point out that reinfection studies in higher-risk populations cover people who were not active injectors during the HCV treatment period. The HCV reinfection rate in this study is similar to the community incidence of HCV in Scotland.
“The high HCV incidence and reinfection rates highlight the failure of current coverage and intensity of harm reduction interventions to minimize injecting risk,” say the investigators. The population would benefit from “a broader programme of social and psychological interventions […] to reduce injecting risk.”
The high reinfection rate “demonstrates that we have successfully engaged with and treated a high-risk injecting population who should be targeted as part of any successful treatment as prevention (TasP) strategy,” the researchers conclude.
In an accompanying Comment article, Professor Greg Dore of the Kirby Intsitute, University of New South Wales, Sydney, said that modelling of treatment uotake in Australia suggests that reinfection rates among people who inject drugs can be expected to rise until 2023 if Australia continues to achieve high rates of treatment among drug users, before beginning to decline as the number of people who inject drugs with chronic HCV infection begins to decline substantially.
“Intensive injecting network exploration and screening could be utilised for those who develop HCV reinfection,” he says, noting that sexual partners are often injecting partners too. Ongoing monitoring of reinfection, point-of-care technologies that can detect HCV RNA – such as fingerprick sampling – and rapid initiation of treatment will all contribute to efforts to reduce reinfection in people who use drugs.
By Keith Alcorn
Schulkind J et al. High response and re-infection rates among people who inject drugs treated for hepatitis C in a community needle and syringe programme. J Viral Hepat, 2018: 1-10.