Injection Drug Use and Immunodeficiency Linked to Failed Hepatitis C Treatment in People with HIV

New research is shining light on the efficacy of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) in people with human immunodeficiency virus (HIV), highlighting a 95% treatment success rate in this patient population and providing additional insight into factors negatively affecting treatment response.¹

Leveraging data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), the study found that although unsuccessful HCV treatment with DAAs was uncommon, it was more frequently observed among people with lower CD4+ cell counts, people with HCV genotype 4, and people who reported recently injecting drugs.¹

According to the World Health Organization, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring per year. While the advent of DAAs has introduced an effective option for achieving HCV cure in many patients, treatment is not successful for an estimated 5% of infected individuals.² Historically, successful HCV treatment has been even less common among people with HIV, especially in the era of interferon-based regimes, but DAA treatment has introduced greater cure rates even in this difficult-to-treat population.¹

“While 95% of people with HIV/HCV being successfully treated is encouraging, there is a need to understand why a small proportion of these people are unsuccessfully treated,” Brendan Harney, PhD, MPH, a postdoctoral research fellow at the University of Montreal Hospital Center (CHUM) and research officer at Burnet Institute, and colleagues wrote.¹ “This is important at an individual level due to the potential development and/or progression of liver disease and for public health due to potential transmission, which may have implications for global targets of reductions in HCV-related mortality and incidence, respectively.”

To examine characteristics linked to an increased probability of unsuccessful DAA HCV treatment, investigators examined data from the InCHEHC, which was pooled data from cohorts of people with HIV using a protocol based on the HIV Cohort Data Exchange Protocol (HICDEP). Data were available for patients from Australia, Canada, France, The Netherlands, Spain, and Switzerland up to the end of 2019.¹

The present study included people who initiated interferon-free DAA HCV treatment between 2014 and 2019, excluding those who did not have adequate follow-up time to ascertain cure outcomes. For the purpose of analysis, investigators defined unsuccessful treatment as a positive HCV RNA test at a patient’s first RNA test ≥ 4 weeks (SVR4+) following the end of treatment.¹

Overall, 4542 people had DAA treatment data recorded, of whom 4502 (99.1%) had HCV RNA and/or SVR-related data recorded at least once. Among these patients, 4468 (99.2%) had sufficient follow-up time for outcome ascertainment.¹

Among the cohort, the majority of patients were male (81.3%) with a mean age of 50 (range, 21–85; Standard deviation [SD], 8.9) years. Investigators noted 44.4% of participants were defined as gay or bisexual males and 25.6% were males with a history of injection drug use.¹

Of the 4468 people who commenced DAA treatment, 4098 (91.7%) had an SVR test ≥ 4 weeks following the end of treatment. In total, 207 (5.0%) participants met the criteria for unsuccessful treatment, 62.3% of whom were classified as relapse and 37.7% of whom were classified as nonresponse.¹

Upon analysis, compared with a CD4+ cell count > 500 cells/mm3, cell counts < 200 (adjusted odds ratio [aOR], 1.81; 95%CI, 1.00–3.29) and between 200 and 349 (aOR, 1.95; 95% CI, 1.30–2.93) were associated with increased odds of unsuccessful treatment. Investigators additionally pointed out HCV genotype 4 was associated with increased odds of unsuccessful treatment compared with genotype 1 (aOR, 1.56; 95% CI, 1.04–2.32).¹

Among 1921 participants with data on injection drug use in the 12 months prior to treatment, 1780 (92.7%) had an SVR4+ test, of whom 94 (5.3%) were unsuccessfully treated. Investigators called attention to evidence suggesting recent injection drug use was associated with increased odds of unsuccessful treatment but were careful to note that this association did not reach statistical significance (aOR, 1.67; 95% CI, 0.99–2.82).¹

They outlined multiple limitations to these findings, including a lack of data on treatment adherence and factors potentially influencing adherence; difficulties differentiating between unsuccessful treatment due to relapse and reinfection post-treatment but before SVR is confirmed; the retrospective pooled nature of the data; and the potential lack of generalizability to low- and middle-income countries or those without universal healthcare systems.¹

“In this large, international multi-cohort collaboration, consistent with clinical trials and other observational studies, approximately 5% of people living with HIV who commenced DAA treatment had unsuccessful HCV treatment,” investigators concluded.¹ “While uncommon, unsuccessful treatment was associated with low absolute CD4+ cell counts and recent injection drug use. Extra support and monitoring through HCV treatment may be warranted among some people who report recent injection drug use and people with low CD4+ cell counts.”

References

1. ^{Harney BL, Sacks-David R, van Santen DK, et al. Unsuccessful Direct Acting Antiviral Hepatitis C Treatment Among People With HIV: Findings From an International Cohort. Liver International. https://doi.org/10.1111/liv.16203}

2. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed December 12, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}