Therapeutic strategies for recent hepatitis C virus infection in the era of direct-acting antiviral therapy

Download files
Access & Terms of Use
open access
Copyright: Martinello, Marianne
Altmetric
Abstract
Background: The management of recent hepatitis C virus (HCV) infection is uncertain, as the therapeutic landscape evolves with the advent of direct-acting antiviral (DAA) therapy. Aims: The broad aim of this research was to examine novel therapeutic strategies in recent HCV following the availability of DAA therapy. Specific aims included assessing the feasibility, efficacy and safety of response-guided interferon (IFN)-containing and ultra-short IFN-free therapy; calculating reinfection incidence following treatment; and determining the clinical significance of drug-drug interactions in HIV/HCV co-infection. Methods: In Chapters Two and Three, the efficacy and safety of short and/or response-guided treatment among individuals with recent HCV was examined in three open-label trials: ATAHC II (n=52; pegylated-IFN +/- ribavirin), DARE-C I (n=14; pegylated-IFN, ribavirin + telaprevir) and DARE-C II (n=19; sofosbuvir + ribavirin). In Chapter Four, reinfection incidence following treatment for recent HCV was calculated among those who achieved an end-of-treatment response in ATAHC I and II, DARE-C I and II (n=120). In Chapter Five, a simulation of potential drug-drug interactions between combination antiretroviral therapy and DAAs was performed in those with HIV/HCV enrolled in CEASE-D (n=257). Key Findings: A total of 85 individuals (73% HIV) with recent HCV commenced short and/or response-guided treatment between 2010 and 2015; none of the strategies trialled was optimal. Given toxicity, the applicability of an IFN-containing strategy is limited. Conversely, six weeks of sofosbuvir and ribavirin was safe and well tolerated, but efficacy was poor. High reinfection incidence, particularly in individuals reporting injection drug use following treatment, was seen. These trials confirmed the feasibility of short duration therapy in recent HCV and informed contemporary trial design. Optimal DAA regimen choice for future research will be crucial; the combination of a nucleotide analogue and an NS5A inhibitor appears appropriate given potency and little potential for drug-drug interactions in HIV/HCV co-infection. Conclusion: The role and efficacy of ultra-short duration therapy in recent HCV requires further evaluation with potent DAA regimens. The significant risk for HCV reinfection following treatment in individuals with ongoing behaviour facilitating transmission emphasises the need for post-treatment surveillance, harm reduction strategies and education.
Persistent link to this record
Link to Publisher Version
Link to Open Access Version
Additional Link
Author(s)
Martinello, Marianne
Supervisor(s)
Matthews, Gail
Dore, Gregory
Creator(s)
Editor(s)
Translator(s)
Curator(s)
Designer(s)
Arranger(s)
Composer(s)
Recordist(s)
Conference Proceedings Editor(s)
Other Contributor(s)
Corporate/Industry Contributor(s)
Publication Year
2017
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
Files
download public version.pdf 2.27 MB Adobe Portable Document Format
Related dataset(s)