title: Mixed HCV infection and reinfection in people who inject drugs--impact on therapy.
abstract: The majority of new and existing cases of HCV infection in high-income countries occur among people who inject drugs (PWID). Ongoing high-risk behaviours can lead to HCV re-exposure, resulting in mixed HCV infection and reinfection. Assays used to screen for mixed infection vary widely in sensitivity, particularly with respect to their capacity for detecting minor variants (<20% of the viral population). The prevalence of mixed infection among PWID ranges from 14% to 39% when sensitive assays are used. Mixed infection compromises HCV treatment outcomes with interferon-based regimens. HCV reinfection can also occur after successful interferon-based treatment among PWID, but the rate of reinfection is low (0-5 cases per 100 person-years). A revolution in HCV therapeutic development has occurred in the past few years, with the advent of interferon-free, but still genotype-specific regiments based on direct acting antiviral agents. However, little is known about whether mixed infection and reinfection has an effect on HCV treatment outcomes in the setting of new direct-acting antiviral agents. This Review characterizes the epidemiology and natural history of mixed infection and reinfection among PWID, methodologies for detection, the potential implications for HCV treatment and considerations for the design of future studies.
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Evan B
authors.initials: EB
authors.lastname: Cunningham
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Applegate
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy / Q000453:epidemiology*; D014943:Global Health / Q000706:statistics & numerical data; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D015995:Prevalence; D012008:Recurrence; D012307:Risk Factors; D015819:Substance Abuse, Intravenous / Q000453:epidemiology*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007372:Interferons