Rapid Treatment of HCV for People Who Inject Drugs to Increase Cure Rates
Supported by an educational grant from Gilead Sciences, Inc.
Mark S. Gold, MD
“I’ve been impressed with the urgency of doing. Knowing is not enough; we must apply. Being willing is not enough, we must do.” -Leonardo da Vinci
The last installment of the Research You Can Use series focused on research related to hepatitis C virus (HCV) in people who inject drugs (PWID), a growing cohort of younger individuals fueling a steady increase in HCV infections [1]. Young PWID have higher HCV incidence and lower treatment rates compared to their older peers [2]. In that report, I analyzed a recent systematic review from Grebely and colleagues that demonstrated that recent treatment for opioid use disorder (OUD) was associated with improvements in testing and treatment uptake among PWID, supporting the integration of HCV services in drug treatment centers [2]. Continuing with the theme of urgency and opportunity, I would like to share results from a poster presented at the recent Infectious Disease Week (IDWeek 2021) and The Liver Meeting Digital Experience in collaboration with the American Association for the Study of Liver Diseases (AASLD) entitled Rapid Hepatitis C Treatment Initiation in Young People Who Inject Drugs: Final Results from the HCV-Seek, Test & Rapid Treatment (HCV-ST&RT) Randomized Pilot Clinical Trial, led by Benjamin Eckhardt, MD, MS, Assistant Professor, Department of Medicine at NYU Langone School of Medicine [3].
Between October 2018 and March 2020, with 1-year follow-up periods through March 2021, Eckhardt and colleagues recruited PWID age 18-29 who had injected drugs within the past 30 days. Eligible participants who were HCV antibody positive and treatment naïve were randomized 1:1 to the Rapid Treatment arm or the Usual Care arm. Those randomized to the Rapid Treatment arm received same-day medical evaluation, confirmatory and baseline testing, and a 7-day starter pack of sofosbuvir/velpatasvir (SOF/VEL). Participants in the Usual Care arm received same-day HCV confirmatory testing, which, if positive, facilitated referral to local providers. The primary endpoint was sustained virologic response (SVR12) in RNA-positive participants within 12 months of enrollment [3].
Thirty-eight PWID were enrolled and randomized in the clinical trial. Fourteen of 18 in the Rapid Treatment arm and 11 of 20 in the Usual Care arm met the criteria of HCV RNA positive and were included in the intention-to-treat analysis. Demographics were similar among the cohorts:
· Mean age of 26
· 24% women
· 36% Hispanic, 4% non-Hispanic Black
· 24% were homeless, at baseline
· 52% received medication for OUD in the prior 90 days
· Participants injected a median of 20 of the last 30 days
In the intention-to-treat analysis, 64% (9/14) of PWID in the rapid treatment arm achieved SVR12. In the Usual Care arm, 18% (2/11) had confirmed SVR12. Of the individuals in the Rapid Treatment arm who did not achieve SVR12, one had treatment failure, one did not start treatment, one had an on-treatment response with pending SVR confirmation, and two were lost to follow-up. The difference between on-site Rapid Treatment compared to Usual Care outside referral achieved statistical significance (p = .042), underscoring the importance of seizing the opportunity to treat PWID with urgency when the opportunity presents [3].
The AASLD and the Infectious Diseases Society of America (IDSA) have recommended that patients with HCV be assessed with a simplified treatment algorithm that uses standard blood and fibrosis tests, rather than genotype testing, to guide initiation of pangenotypic direct-acting antivirals (DAAs) SOF/VEL or glecaprevir/pibrentasvir treatment. Because of the ease of use of DAAs, the AASLD/IDSA guidance broadens treatment beyond specialists and states that patients with HCV can be managed by non-specialist health care professionals (HCPs) [4]. Majethia and colleagues evaluated the economic impact of this simplified treatment approach and found that access to treatment from a broader range of specialists and non-specialist HCPs recognized cost savings from fewer office visits, less outpatient care, and fewer laboratory services and other non-inpatient and emergency department services, supporting treatment of all patients with HCV [5].
Stigma continues to be a barrier to seeking treatment among PWID with HCV. Studies have found that 95% of patients with HCV have experienced some degree of perceived disease-related stigma [6]. There is a need for education from HCPs to PWID that addresses misinformation and patient-level knowledge in order to reduce HCV-associated stigma and to increase patient engagement in HCV care. Between July 2018 and May 2019, Saine and colleagues conducted a cross-sectional study of adults age 18 (n = 265) with a history of HCV infection. One of the participating sites was housed within a syringe service program where patients were also undergoing activity treatment for substance use disorder. Participants answered HCV knowledge-based questions about HCV transmission and natural history, and 80% answered > 80% of the questions correctly. Contrary to the study hypothesis, the greater the HCV knowledge of transmission and natural history, the greater the HCV stigma. The authors posed several reasons for this, including greater awareness of disease stereotypes, social stigmas, and the resulting effects of HCV infection on social and interpersonal interactions, contributing to greater levels of stigma. Fear may reduce opportunities for social support and increased shame [7]. In addiction medicine, the disease model of addiction (based on the idea that it is a brain disease) has reduced stigma, and many programs teach families and patients how drugs work and addict by using brain models that have been developed. All of our experiences have confirmed that knowledge and education allow self-acceptance, reduce denial, and improve family and community support. HCV stigma interventions should be targeted in a different way.
Awareness of this stigma should spur HCPs to allot time for education to dispel common misconceptions and counterbalance stigma. Referrals to behavioral specialists and/or peer support groups may be helpful for many patients as a safe venue to discuss their personal feelings and interactions as part of a holistic approach to HCV disease management [7].
Barriers to testing and treatment of PWID for HCV are multi-factorial. Achieving a cure and optimal long-term outcomes in this vulnerable patient population requires urgency and opportunity—meeting patients where they live, seizing the opportunity to initiate rapid treatment, and educating patients to counter stigma and social isolation.
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Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food.
References
1. Centers for Disease Control and Prevention [CDC]. Viral hepatitis surveillance—United States, 2019. CDC Website. https://www.cdc.gov/hepatitis/statistics/2019surveillance/index.htm. Published July 2021. Accessed December 14, 2021.
2. Grebely J, Tran L, Degenhardt L, et al. Association between opioid agonist therapy and testing, treatment uptake, and treatment outcomes for hepatitis C infection among people who inject drugs: a systematic review and meta-analysis. J Clin Infect Dis. 2021;73(1):e107-e118.
3. Eckhardt B, Kapadia S, Smith M, et al. Rapid hepatitis C treatment initiation in young people who inject drugs: final results from the HCV-seek, test & rapid treatment (HCV-ST&RT) randomized pilot clinical trial. Presented at: IDWeek; September 29 to October 3, 2021. Poster 911.
4. AASLD-IDSA HCV Guidance Panel Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67(10):1477-1492.
5. Majethia S, Lee IH, Chastek B, et al. Economic impact of the AASLD-IDSA simplified treatment algorithm on the real-world management of hepatitis C. J Manage Care Spec Pharm. 2021 Oct 22;1-10. [Epub ahead of print].
6. Saine ME, Szymczak JE, Moore TM, Bamford LP, Barg FK, Schnittker J, et al. Determinants of stigma among patients with hepatitis C virus (HCV) infection. J Viral Hepat. 2020;27(11):1179-1189.
7. Saine ME, Szymczak JE, Moore TM, et al. The impact of disease-related knowledge on perceptions of stigma among patients with hepatitis C virus (HCV) infection. PLoS One. 2021;16(10):e0258143.