Illicit Fentanyl Use Independently Predicts HCV Seroconversion Among a Cohort of People Who Inject Drugs in Tijuana and San Diego

Background Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts HCV and HIV incidence among a cohort of people who inject drugs (PWID) in San Diego, CA and Tijuana, Mexico. Methods PWID were recruited into a prospective cohort in two waves during 2020-2022, undergoing semi-annual interviewer-administered surveys, HIV and HCV serology through February 2024. Cox regression was conducted to examine predictors of seroconversion considering self-reported IMF use as a fixed or lagged, time-dependent covariate. Results Of 398 PWID at baseline, 67% resided in San Diego, 70% were male, median age was 43, 42% reported receptive needle sharing and 25% reported using IMF. Participants contributed a median of 6 semi-annual study visits (IQR:4-6). HCV incidence was 14.26 per 100 person-years (95% CI: 11.49-17.02), and HIV incidence was 1.29 (1.00-2.28). IMF was associated with HCV seroconversion, with a univariable hazard ratio (HR) of 1.68 (95%CI: 1.12-2.53) which remained significant in multivariable models (adjHR1.54; 95%CI:1.01-2.34). The direction of the relationship with HIV was similar, albeit not significant, with an HR of 2.53 (0.7-9.15). Conclusion We document a novel association between IMF and HCV seroconversion among PWID in Tijuana-San Diego. There was insufficient power to detect if a similar relationship held for HIV. IMF’s short half-life may destabilize PWID— increasing the need for repeat dosing and sharing smoking materials and syringes. Tailoring medication dosing for opioid use disorder and new preventative care approaches may reduce HCV transmission in the fentanyl era. Summary In this cohort study of people who inject drugs in Tijuana, Mexico, and San Diego, California, fentanyl use was independently associated with HCV seroconversion. Tailored treatment and prevention efforts are needed for patients using fentanyl to minimize blood-borne infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the San Diego Center for AIDS Research (National Institute of Allergy and Infectious Diseases, grant P30AI036214) and the National Institute on Drug Abuse (grants R01DA049644-S1, R01DA049644-02S2, K01DA043412, 3K01DA043412-04S1, DP2DA049295, and T32DA023356). JRF was supported by the National Institute of General Medical Sciences (grant GM008042). WHE received funding from NIDA T32 DA023356. BS received funding from K01DA049665 and R03 DA57142. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Boards at the University of California San Diego, in the United States and Universidad Xochicalco in Tijuana, Mexico gave ethical approval for this work. All participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The underlying data used in this study are protected as part of a cohort study of vulnerable individuals. Aggregated statistics may be requested from the authors on a case-by-case basis.