Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study.

BACKGROUND: In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment. METHODS: SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016-2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations. RESULTS: At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test-Consumption; range, 1-12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.99) and sharing (OR, 0.87; 95% CI, 0.80-0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94-1.02) or alcohol use (OR, 0.99; 95% CI, 0.95-1.04). CONCLUSIONS: Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use. CLINICAL TRIALS REGISTRATION: SIMPLIFY, NCT02336139; D3FEAT, NCT02498015.

Opioid agonist treatment dosage and patient-perceived dosage adequacy, and risk of hepatitis C infection among people who inject drugs.

BACKGROUND: Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in opioid agonist treatment is unclear. We investigated the joint association of prescribed dosage of opioid agonist treatment and patient-perceived dosage adequacy with risk of HCV infection among people who inject drugs. METHODS: We followed prospectively people who inject drugs at risk of acquiring HCV infection (who were RNA negative and HCV-antibody negative or positive) in Montréal, Canada (2004-2017). At 6-month, then 3-month intervals, participants were tested for HCV antibodies or RNA, and completed an interviewer-administered behavioural questionnaire, reporting the following: current exposure to opioid agonist treatment (yes/no), prescribed dosage either high (methadone ≥ 60 mg/d or buprenorphine ≥ 16 mg/d) or low, and perceived dosage adequacy (adequate/inadequate). We then assigned participants to 1 of 5 exposure categories: no opioid agonist treatment, high dosage of opioid agonist treatment perceived to be adequate, high dosage perceived to be inadequate, low dosage perceived to be adequate or low dosage perceived to be inadequate. To estimate associations between categories of opioid agonist treatment dosage and incident HCV infection, we conducted Cox regression analyses, adjusting for multiple confounding factors. RESULTS: Of 513 participants (median age 35.0 yr, 77.6% male), 168 acquired HCV over 1422.6 person-years of follow-up (incidence 11.8/100 person-years, 95% confidence interval [CI] 10.1-13.7). We observed a gradient in the relative risks of HCV infection across categories of opioid agonist treatment dosage. Compared with people who inject drugs not receiving opioid agonist treatment, adjusted hazard ratios were 0.43 (95% CI 0.23-0.84) for those receiving high dosages perceived to be adequate, 0.61 (95% CI 0.25-1.50) for those receiving high dosages perceived to be inadequate, 1.22 (95% CI 0.74-2.00) for those receiving low dosages perceived to be adequate and 1.94 (95% CI 1.11-3.39) for those receiving low dosages perceived to be inadequate. INTERPRETATION: Risk of HCV infection varies considerably according to dosage of opioid agonist treatment and patient-perceived adequacy, with associations indicating both protective and harmful effects relative to no exposure to opioid agonist treatment.

Harm Reduction Coverage and Hepatitis C Incidence: Findings From a Cohort of People Who Inject Drugs.

INTRODUCTION: Needle and syringe programs and opioid agonist therapy are essential for harm reduction among people who inject drugs. Few studies assess their combined potential in preventing hepatitis C virus infection. No studies have assessed whether they perform similarly among individuals at risk of primary and recurrent infection. This study aimed to estimate the rates of hepatitis C virus acquisition according to harm reduction coverage among hepatitis C virus-naive and previously infected people who inject drugs in Montreal, Canada. METHODS: This prospective cohort study involved regular interviews and hepatitis C antibody and RNA testing (data collection: 2010-2017, analysis: 2018). Opioid agonist therapy coverage was defined by current dose: high (≥60 mg/day methadone, ≥16 mg buprenorphine), low, or none. Complete needle and syringe program coverage was defined as exclusively reporting safe needle and syringe sources (past 6 or 3 months). Combined coverage was defined as full (high-dose agonist/complete needle/syringe coverage), minimal (low-dose agonist/incomplete needle/syringe coverage), and partial (remaining combinations). Cox regression models were fit. RESULTS: A total of 106 events were observed over 1,183.1 person-years for primary and recurrent incidence rates of 10.6 (95% CI=8.0, 13.8) and 7.6 (95% CI=5.6, 9.9) per 100 years, respectively. High-dose opioid agonist therapy was associated with a 77% reduction in hepatitis C virus acquisition (hazard ratio=0.23, 95% CI=0.10, 0.50) compared with not receiving opioid agonist therapy. Needle and syringe coverage was not associated with infection rates. Estimates considering their combination reflected opioid agonist therapy coverage. Associations were similar among hepatitis C virus-naive and previously infected people who inject drugs. CONCLUSIONS: High-dose opioid agonist therapy seems particularly important to reduce drug-related harms among hepatitis C virus-naive and previously infected people who inject drugs in Montreal.