Table 1 describes the sample characteristics of the study participants. Of 4094 eligible PWID included in this analysis, 2258 (55.2%) were anti-HCV positive; anti-HCV prevalence was 42.1% among young PWID and 62.2% among older PWID. Anti-HCV positivity was significantly higher among PWID who were black (58.6%), >35 years of age (62.2%), with a high school diploma/General Education Development diploma (GED) or less (57.3%), reported injecting speedball (mixture of heroin and cocaine) (72.0%) or heroin (55.9%) most frequently compared to other drugs (40.8%) (powder cocaine, crack cocaine, amphetamines, pain medication, etc), reported receptive syringe sharing (61.4%), shared injection equipment (60.1%), and injected more than once a day (57.8%). There were no other significant differences in antiHCV positivity.

Table 2 describes PWID self-reported hepatitis C testing and care characteristics by anti-HCV test result. Approximately 87.2% of anti-HCV positive and 69.2% of anti-HCV negative PWID reported that they had been previously tested for hepatitis C before their NHBS interview. Among anti-HCV positive PWID, they self-reported that the most common locations of the last hepatitis C test were public health clinics/community health centers (38.0%) and correctional facilities (18.7%). Public health clinic/community health center (29.3%) was also the most common location of the last hepatitis C test among anti-HCV–negative PWID. Among all anti-HCV–positive PWID who were previously informed of their HCV infection by a healthcare provider, 19.2% were treated.

Past or present HCV infection prevalence among PWID in this sample was high and varied by age. Anti-HCV positivity was 42% and 62% among young PWID and older PWID, respectively. The higher prevalence among older PWID was expected, as this group is likely to have been injecting for a longer period and therefore more likely to have been exposed to HCV. The anti-HCV positivity among young PWID in this analysis is consistent with a prevalence of 33%–48% among young PWID reported in other studies [7, 17, 18]. Common to both young and older PWID, those who reported having a high school diploma/GED or less were more likely to be anti-HCV positive compared to those with a higher level of education. Previous studies have found that PWID with a lower educational level are more likely to engage in hepatitis C risk behaviors and be unaware of risk-reduction practices [19, 20]. Sharing injection equipment in the past 12 months was a significant correlate of anti-HCV positivity among young and older PWID. Although sharing injection equipment like cookers, filter, or water is a known hepatitis C risk factor [21], many PWID are not aware of its transmission risk or perceive this risk to be very low [22]. Furthermore, many hepatitis C prevention interventions do not emphasize injection equipment sharing as a risk factor for HCV transmission as strongly, as they emphasize the risk associated with syringe and needle sharing [22]. These factors may account for the high prevalence of injection equipment sharing among both young and older PWID and its association with anti-HCV positivity in both age groups.

Receptive syringe sharing in the past 12 months was associated with anti-HCV positivity among young PWID. Social factors and relationships influence syringe sharing behaviors among young PWID. Young PWID usually start injecting within sexual or social networks that can foster needle and syringe sharing behaviors [23, 24]. Perceptions of trust and diminished perceptions of personal and syringe sharing partner risk can drive these behaviors among young PWID [23–25]. New injectors have little hepatitis C risk knowledge and may buy, prepare, divide, and inject drugs in group settings where needle, syringe, and injection equipment sharing are common [25]. Many young PWID may have limited or no access to syringe service programs (SSPs) [26]. This can hinder their access to sterile needles and syringes and further facilitate sharing. Receptive syringe sharing was not associated with anti-HCV positivity among older PWID in this analysis. The transmission risks associated with needle and syringe sharing have been disseminated and emphasized in HIV prevention interventions since early in the HIV epidemic [22]. Therefore, generational experiences and first-hand knowledge of the transmission risk of HIV and other blood-borne pathogens through syringe sharing among older PWID may explain the age-related differences in this behavior [13].

Frequently injecting speedball was associated with anti-HCV positivity in young and older PWID compared to heroin. Speedball is a combination of heroin and cocaine and is associated with an intense euphoric effect when injected, compared with other drugs [27]. This effect increases dependence and injection frequency among its users, which in turn increases hepatitis C risk [21, 28]. Arrest history in the past 12 months was associated with anti-HCV positivity among young PWID but not older PWID. Young people are arrested more often than older people [29], and hepatitis C risk behaviors such as needle and syringe sharing for drug use, tattoos, and piercings are prevalent in correctional settings [30]. A recent arrest can also deter PWID from accessing SSPs for sterile needles and syringes [7, 31]. Given the burden of HCV infection among PWID, comprehensive hepatitis C prevention interventions such as hepatitis C testing and risk-reduction education programs, expanding access to SSPs and medication-assisted therapy (MAT) for opioid use disorder, and treatment of HCV-infected (HCV RNA positive) PWID are urgently required.

Approximately 19% of all PWID in this analysis reported that they had not been previously tested for hepatitis C before the NHBS interview despite the recommendation by the US Preventive Services Task Force [32]. Expanding hepatitis C testing, including follow-up diagnostic testing of an anti-HCV–positive person with HCV RNA testing, is important to identify and link currently HCV-infected PWID to care and provide an opportunity to educate PWID on hepatitis C risk and risk-reduction behaviors. Educating young PWID on hepatitis C risk is especially important because the greatest risk of HCV infection is during the first few years after initiating injection [33], and many report hepatitis C risk behaviors and little knowledge of safer injection practices [7, 25]. Education interventions should also recognize the influence of social networks on injection-risk behaviors [24] and address this by promoting peer norms that discourage risky injection practices.

SSPs and MAT are effective interventions that can reduce HCV transmission risk [34–37]. SSPs provide access to sterile needles and syringes at no cost and facilitate safe needle and syringe disposal. Access to SSPs is associated with reduction in injection-related risk behaviors among PWID [34]. In addition, comprehensive programs can often provide hepatitis C testing and education and referral to MAT and hepatitis C treatment programs. MAT involves the use of opioid agonists such as buprenorphine and methadone in combination with behavioral therapy for opioid use disorder treatment [36, 37]. Opioid agonists activate opioid receptors, preventing withdrawal, drug craving, and reducing injection frequency, thereby decreasing hepatitis C acquisition risk. Although MAT is associated with a 60% reduction in incident HCV infections in PWID [37], access remains low in the United States [38]. Strategies such as increasing the availability of comprehensive SSPs that provide MAT services and improving insurance coverage and benefits that mitigate out-of-pocket costs for buprenorphine and methadone can improve access to MAT.

Treating HCV-infected PWID with direct-acting antivirals (DAAs) is another effective hepatitis C prevention and control strategy [39]. A systematic review of studies examining DAA treatment for HCV infection among PWID showed that 97.5% completed the treatment regimen and 87.7% achieved sustained virologic response (cure) [40]. Modeling studies have shown that rapidly scaling up DAA treatment for HCV-infected PWID can greatly reduce hepatitis C prevalence and incidence [39]. However, most HCV-infected PWID do not receive treatment [41, 42]. High drug prices, state Medicaid policies and insurance restrictions, lack of insurance, and some providers’ ignorance about treatment guidelines for PWID or reluctance to offer DAA treatment to PWID because of concerns about treatment adherence and posttreatment reinfections remain barriers to treatment [41, 43]. Policies that reduce treatment costs, rapidly scale up hepatitis C treatment for uninsured or underinsured PWID to reduce reinfection risk, reform restrictive health insurance policies, and educate providers about the benefits of treating all HCV-infected PWID and the high treatment response and adherence rates among PWID can mitigate these barriers [40, 42].

There are several limitations to this analysis. First, we did not test for current infection with HCV RNA. Some individuals testing positive for anti-HCV could have been effectively treated, and others (approximately 15%–25%) may have been infected and cleared the virus naturally [44]. Second, the findings from this analysis may not be generalizable to all PWID because the participants are not a representative sample of all PWID. Third, our findings are based on self-reported data and might be subject to social desirability and recall bias, which may affect the estimation of injection and preventive behaviors. Fourth, data were obtained from 2015; it is possible that the burden of hepatitis C among PWID may have changed since then. Last, because respondent-driven sampling methodology relies on recruitment through social networks, PWID who inject alone or rarely interact with other PWID may not be sampled.

In conclusion, anti-HCV positivity among young and older PWID in this sample is high. Given the current opioid crisis, it is likely that HCV infection attributable to injection drug use will continue to increase, particularly among young PWID. Education about hepatitis C risk behaviors and expanding hepatitis C testing is essential to identify HCV-infected PWID. Combination hepatitis C prevention interventions such as SSPs, MAT, and DAA treatment for infected PWID are effective in reducing HCV transmission risk and disease burden among PWID. Access to effective DAA treatment in particular must be improved, otherwise it can limit the effectiveness of other prevention approaches like MAT and SSP [45]. Scaling up these HCV prevention interventions and addressing the system-level barriers that affect access to them is critical to their effectiveness.