Hepatitis C (HCV) is a global pandemic. The World Health Organization has developed a strategic plan for HCV elimination that focuses on low- and middle-income countries (LMICs) and high-risk populations, including people who inject drugs (PWID). While direct-acting antiviral (DAA) therapies are highly effective at eliminating HCV infections and have few side effects, medical professionals and policymakers remain concerned about the risk of reinfection among PWID. This study is a systematic review of research measuring the rate of HCV reinfection among PWID in LMICs and identifies additional areas for further research. A systematic search strategy was used to identify studies documenting HCV reinfection after sustained virologic response in PWID in LMICs. We refined results to include studies where at least 50% of participants had DAA treatment for primary HCV infection. Pooled reinfection rate was calculated across all studies. Seven studies met eligibility criteria. Most studies were conducted in six upper middle-income countries (Mexico, Romania, Russia, Taiwan, Georgi, and Brazil) and one lower middle-income country (Bangladesh) with a total of 7665 participants. No study included information from PWID in low-income countries. Sample sizes ranged from 200 to 3004 individuals, with demographic data missing for most participants. Four studies used deep gene sequencing, and reflex genotyping procedures to differentiate reinfection (infection by a different HCV genotype/subtype) from virologic relapse (infection by the same strain). The follow-up time of people cured from primary chronic HCV infection ranged from 12 weeks to 6.6 years. The pooled reinfection rate of all seven studies was 2.8 (range: 0.02 to 10.5) cases per 100 person-years (PY). In the five studies that differentiated relapse from reinfection, the incidence of reinfection was 1.0 per 100 PY. To date, research on reinfection rates among PWID in LMICs remains limited. Research focused on PWID in low-income countries is particularly needed to inform clinical decision making and evidence-based programs. While rates of reinfection among PWID who complete DAA treatment in upper and lower middle-income countries were similar or lower than rates observed in PWID in high-income countries, the rates were highly variable and factors may influence the accuracy of these measurements. This systematic review identifies several areas for continued research. Policies concerning access to HCV testing and treatment should be comprehensive and not place restrictions on PWID in these settings.

Hepatitis C (HCV) disproportionately affects people who inject drugs (PWID). Despite availability of safe and effective treatment, HCV treatment access and uptake among PWID in low- and middle-income countries (LMICs) has been limited. Understanding the lived experiences of PWID in these settings who have undergone treatment provides the opportunity to gain insight into how to implement treatment programs that meet the needs of this population. Using Rhodes’ Risk Environment Framework to guide our work, we conducted semi-structured interviews with 35 PWID who received HCV treatment in methadone clinics and drop-in-centers (DICs) in Nairobi and coastal Kenya supported by peer case managers from August to September 2019. Translated and transcribed interviews were analyzed thematically. Three overarching themes emerged in our thematic analysis: 1) Financial constraints as a barrier to HCV treatment, 2) HCV-related stigma, and 3) HCV treatment impacts on health and risk behaviors. These data signal unique challenges faced by PWID seeking HCV treatment in this LMIC setting and highlight the importance of interventions to reduce barriers to treatment. In order for positive treatment outcomes to be sustained, HCV treatment programs must address the barriers patients face at multiple levels and implement system-level changes.