And Then There Was One: HCV Elimination in the Coinfected Population

The treatment of the hepatitis C virus (HCV) has evolved considerably in the past 15 years. Second-generation direct-acting antivirals entered the market in late 2014. Today we have well-tolerated, short-course (generally 8-12 weeks), pangenotypic options with greater than 95% efficacy to achieve cure or sustained virologic response (SVR). In the World Health Organization’s (WHO) most recent global health sector strategies for 2022 to 2030, it is estimated that the treatment of HCV worldwide increased 10-fold since 2015.¹

Despite these advances, the most recent epidemiologic data for HCV in the United States demonstrate that the number of acute HCV cases has doubled since 2014. Approximately 57% of these cases reported the risk for exposure to HCV as injection drug use (IDU).² There has long been an understanding of the intertwined nature of the HCV and HIV epidemics, which is largely a result of shared risk factors for infection and social determinants of health. In conjunction with sexually transmitted diseases (STDs), they are considered part of a syndemic. Syndemic is defined by the CDC as “a clustering of 2 or more social or health conditions within a population.”³ HIV/HCV coinfection has been identified as an important target population due to the increased risk of liver disease progression including cirrhosis, its complications, and hepatocellular carcinoma compared with monoinfected patients. The mechanism behind disease acceleration in coinfected patients is not fully understood but is believed to be related to HIV immune dysregulation, depletion of gastric CD4 cells, oxidative stress related to both infections, and HIV-induced hepatocyte apoptosis.⁴

IDU prevalence in the United States in 2018 was estimated at 1.5% of the population or 3.7 million people.⁵ Approximately 1.2 million people in the United States have HIV, with new infections in 2021 totaling 32,100. Approximately 8% of the new infections occurred in people who inject drugs (PWID).⁶ Moorman et al reviewed publications between 2005 and 2021 to describe the prevalence of these overlapping epidemics.⁷ Across the studies included, prevalence ranges were quite wide—from 20% to 90%—but may provide helpful insights. Overall, investigators found the prevalence of HCV to be greater than the prevalence of HIV. In coinfected patients, IDU was a more common comorbidity than in those infected only with HIV. Numerous plans are aimed at ending AIDS and HCV by 2030. The overarching plan is published by the WHO and builds upon the 2016-2021 plan.¹

The specific target is to reduce annual new HIV and viral hepatitis cases from 4.5 million as the baseline to less than 500,000. The WHO encourages countries to create their own targeted plans. The United States has used the WHO plan to develop the Viral Hepatitis National Strategic Plan for the United States: A Roadmap to Elimination 2021-2025.⁸ Numerous challenges are identified in the elimination of HCV within the United States; most notable are lack of awareness of infection, testing limitations, barriers to treatment, limited data, and the syndemic nature of HIV, HCV, and STDs. In addition to these challenges, the writers of the plan identify the need to address stigma, discrimination, and social determinants of health to achieve the goals. Within the 2023- 2024 White House budget is funding up to $11.3 billion for a national HCV elimination plan aimed at some of these barriers. Given the barriers identified, meeting these targets may seem impossible; however, microelimination studies can provide us with clues to how this might be possible. The idea of microelimination was first proposed in 2017 as a concept to aid in achieving elimination targets by Lazarus et al.⁹ Microelimination is defined as targeting a particular subpopulation for which treatment delivery has been tailored to maximize adherence and SVR. A review published in 2022 evaluated the literature for studies published after 2013 and utilized a microelimination approach. HIV/HCV coinfection was a target population for 8 microelimination studies.¹⁰ The majority of the studies were conducted in high-income countries. The number of patients who initiated treatment as part of the microelimination studies ranged from 122 to 426, with SVR achieved in 35% to 99% of patients. Two of the microelimination studies were conducted in the United States in HIV clinics with collocated HCV treatment. The SVR rates in the US-based populations were 80% and 97%. In their review of the microelimination literature, Lazarus et al evaluated studies for inclusion of the 4 defined criteria of a successful microelimination strategy: a targeted treatment plan for the subpopulation in question, targets to be achieved within a specific time frame, engagement of multiple stakeholders in the treatment plan, and publishing the results. When looking at the 2 US-based HIV/HCV microelimination studies, it is interesting to note that the study by Rizk et al, in which an SVR rate of 80% was achieved, did not include either targets to be achieved within a specific time frame or engagement of multiple stakeholders.¹¹ In comparison, Falade-Nwulia et al achieved an SVR rate of 97% in their cohort and only lacked targets to be achieved within a specific time frame.¹²

Given the epidemiologic data demonstrating increasing rates of acute HCV driven by IDU and the syndemic nature of the HIV/ HCV epidemics, HCV elimination within the coinfected population also should focus on PWID. A systematic review and meta-analysis were published in 2022 by Cunningham et al to identify interventions successful at improving uptake of testing, linkage to care, and treatment initiation in PWID.¹³ A total of 45 studies were included. One limitation of the meta-analysis was the number of different interventions utilized in the studies that prevented the authors from performing a pooled analysis to evaluate the utility of the intervention. Interventions that could be pooled and provided benefit within the HCV care cascade included patient education, provider care coordination, dried blood spot testing, integrated care, patient navigation or care coordination, and point-of-care antibody testing.

Advances in HCV treatment have been incredible.The thought of elimination in the coinfected population is both exciting and daunting. Useful tools to consider when developing plans include microelimination that utilizes the defined criteria for a successful implementation strategy, patient education, provider care coordination, dried blood spot testing, integrated care, use of patient navigation or care coordination, and point-of-care antibody testing. Other interventions may be beneficial in helping HIV/HCV coinfected patients overcome barriers to treatment; however, more research is needed.

References

1. World Health Organization. Global health sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022-2030. Accessed January 15, 2024. https://www.who.int/publications/i/item/9789240053779
2. Hepatitis C surveillance 2021. CDC. Updated August 7, 2023. Accessed January 15, 2024. https://www.cdc.gov/hepatitis/statistics/2021surveillance/hepatitis-c.htm
3. Ending the HIV epidemic in the U.S. CDC. Updated June 9, 2023. Accessed January 15, 2024. https://www.cdc.gov/endhiv/about-ehe/prevention-care.html
4. Lo Re V, Kallan MJ, Tate JP, et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Ann Intern Med. 2014;160(6):369-379. doi:10.7326/M13-1829
5. Bradley H, Hall EW, Asher A, et al. Estimated number of people who inject drugs in the United States. Clin Infect Dis. 2023;76(1):96-102. doi:10.1093/cid/ciac543
6. U.S. statistics. HIV.gov. Updated December 7, 2023. Accessed January 15, 2024. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics/
7. Moorman AC, Bixler D, Teshale EH, et al. Hepatitis C virus-HIV coinfection in the United States among people who inject drugs: data needed for ending dual epidemics. Public Health Rep. Published online July 22, 2023. doi:10.1177/00333549231181348
8. Viral Hepatitis National Strategic Plan for the United States: A Roadmap to Elimination 2021-2025. Accessed January 15, 2024. https://www.hhs.gov/hepatitis/viral-hepatitis-national-strategic-plan/index.html
9. Lazarus JV, Wiktor S, Colombo M, Thursz M; EASL International Liver Foundation. Micro-elimination — a path to global elimination of hepatitis C. J Hepatol. 2017;67(4):665-666. doi:10.1016/j.jhep.2017.06.033
10. Lazarus JV, Picchio CA, Byrne CJ, et al. A global systematic review of hepatitis C elimination efforts through micro-elimination. Semin Liver Dis. 2022;42(2):159-172. doi:10.1055/a-1777-6112
11. Rizk C, Miceli J, Shiferaw B, et al. Implementing a comprehensive HCV clinic within an HIV clinic: a model of care for HCV micro-elimination. Open Forum Infect Dis. 2019;6(10):ofz361. doi:10.1093/ofid/ofz361
12. Falade-Nwulia O, Sutcliffe CG, Mehta SH, et al. Hepatitis C elimination in people with HIV is contingent on closing gaps in the HIV continuum. Open Forum Infect Dis. 2019;6(10):ofz426. doi:10.1093/ofid/ofz426
13. Cunningham EB, Wheeler A, Hajarizadeh B, et al. Interventions to enhance testing and linkage to treatment for hepatitis C infection for people who inject drugs: a systematic review and meta-analysis. Int J Drug Policy. 2023;111:103917. doi:10.1016/j.drugpo.2022.103917