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.

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…However, other studies suggested that previous spontaneous clearance of HCV infection might not reduce the risk of new infection [142]. Ongoing highrisk behaviors among PWID can lead to repeated exposure to HCV, resulting in reinfection [143]. Although reinfection is common, it does not always lead to persistent infection.…”

“…However, the rate of HCV reinfection might be as low as 0-5 cases per 100 person-years, even among persons who continue injected drug use during and after treatment [143,145,146]. Due to the low reinfection rate and potential clearance after reinfection, antiviral treatment should not be withheld for these populations.…”

Diagnostic and Therapeutic Implications in a Case of Mixed Hepatitis C Virus (HCV) Infection

“…Indeed, dual or MI are rarely detected by standard sequencing, because the simultaneous presence of large quantities of different viruses is usually a transient occurrence. Moreover, standard sequencing can generally detect the prevalent virus; in fact only HCV variants present at the prevalence of > 20% (9). In a short period, one strain is deemed to prevail, either for a less efficient host immunological pressure, or for an intrinsic major fitness.…”

“…Blackard J et al defined coinfection as "infection with > 2 HCV heterologous HCVs simultaneously or within a very narrow period before infection with the first HCV as resulted in an immunological response to that virus", superinfection as "infection with a second HCV after the establishment of persistent HCV infection and development of an immunological response to the first virus", and reinfection as "primary infection that is completely cleared virologically prior to a subsequent, secondary infection with either a homologous or a heterologous HCV" (7). Their prevalence is reported from 5% to 39% in individuals with HCV infection, and considerably higher in injection drug user (IDU) cohorts, or in prison settings than in other at-risk groups such as multiple blood recipients and patients undergoing dialysis (1,8,9). It is suggested that MI can impact the course of the disease, either by boosting hepatocellular injury or by increasing the frequency of exacerbations (1).…”

“…However, methods to detect minority populations within the circulating quasi-species are not yet of widespread use; thus, the overall prevalence of HCV MI may be underestimated (2). Although the next generation sequencing (NGS) technologies offer a more sensitive method to detect minority populations within the circulating quasi-species, allowing distinguishing coinfections and superinfections from reinfections, the latter may be overestimated by standard sequencing due to the poor sensitivity in detection of minor variants (2,9,10). Due to the relative genotype specificity of the new anti-HCV drugs, some concerns are voiced about the effectiveness of treatment in HCV MI, but the question is not yet addressed by guidelines, and no reports are issued on the topic.…”