Associations of hepatitis C virus (HCV) antibody positivity with opioid, stimulant, and polysubstance injection among people who inject drugs (PWID) in rural U.S. communities

Background: People who inject drugs (PWID) in the rural U.S. often inject stimulants, alone or with opioids. The impact of these substance use patterns may influence HCV risk behaviors. This analysis examines the associations of HCV antibody positivity with injecting only opioids, only stimulants (methamphetamine/cocaine), and opioids and stimulants together among rural PWID. Methods: The Rural Opioid Initiative (ROI) consists of eight research sites that enrolled people who use drugs in rural communities in ten U.S. states from 2018 to 2020. This cross-sectional analysis included adult participants who resided in a study area and injected any drug in the past 30 days. The primary outcome was HCV antibody positivity. The exposure of interest was injection drug use classified as only opioids, only stimulants, separate injections of opioids and stimulants, and same-syringe injection of both in the past 30 days. We used multivariable log-binomial regression with generalized linear mixed models to generate prevalence ratios (P.R.) adjusted for demographics, injection history, health insurance, and substance use treatment. Results: Among 3,084 participants enrolled in the ROI, 1,982 met inclusion criteria. Most participants injected opioids and stimulants in the same syringe (34%) or separately (21%), followed by injecting only stimulants (26%), and injecting only opioids (19%). Half (51%) were HCV antibody positive. Compared to people who injected only stimulants, HCV antibody positivity was more prevalent among people who injected opioids alone (aPR=1.62, 95% CI:(1.29-2.03)), injected both opioids and stimulants separately (aPR=1.61, 95% CI:(1.32-1.95)), and in the same syringe (aPR=1.54, 95% CI:(1.28-1.85)). Conclusion: HCV antibody positivity, indicating prior exposure, was highest among those who had recently injected opioids, alone or with stimulants. Additional nucleic acid testing is necessary to confirm active infection. More research is needed to determine the underlying causes of HCV antibody positivity by injection use.