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HCV reinfection incidence among individuals treated for recent infection.

ABSTRACT: One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core-E2 and/or NS5B regions. Reinfection incidence was calculated using person-time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV-positive men-who-have-sex-with-men (53%) and people who inject drugs (current 49%, ever 69%). Total follow-up time at risk was 135 person-years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post-treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post-treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post-treatment surveillance, harm reduction strategies and education in at-risk populations.

SUBMITTER: Martinello M

PROVIDER: S-EPMC5400730 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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HCV reinfection incidence among individuals treated for recent infection.

Martinello M M Grebely J J Petoumenos K K Gane E E Hellard M M Shaw D D Sasadeusz J J Applegate T L TL Dore G J GJ Matthews G V GV

Journal of viral hepatitis 20170123 5

One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequenci ...[more]

PMID: 28027424

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Project description:Hepatitis C virus (HCV) remains a significant public health threat as new 1.75 million HCV infections emerged worldwide. The majority of these infections become persistently infected, while around 30 % spontaneously eliminate the virus. Clinical factors for viral clarification are related to HCV interaction with host immune system, but little is known about the consequences after HCV spontaneous resolution. These individuals are difficult to recruit and study as acute infection is usually asymptomatic, and they will not be identified unless it progress to chronic infection. The study of peripheral blood mononuclear cells (PBMCs) of these patients is crucial, as PBMCs are one of the main HCV extrahepatic reservoirs, and its transcriptional profile provide us information of innate and adaptive immune response against HCV infection. Our research shows novel insight on molecular consequences of spontaneous resolution after an acute HCV infection. 96 Individuals with different HCV exposure status were recruited: spontaneous resolved, chronic infected and healthy controls; and the microRNA profile of their PBMCs were analyzed. Our results indicate similar disruption of miRNA expression on HCV chronic patients and those who spontaneously clarified the infection, compared to control patients. The disrupted miRNAs formed a signature of 21 miRNAs that mainly regulate lipid metabolism. This is the first report showing miRNA profile similarities between chronic HCV patients and spontaneous resolved individuals. Thus, our results suggest that HCV infection promotes molecular alterations in PBMCs that will last longer after HCV spontaneous eradication. This evidences open up new prospects in the management of individuals who spontaneously clarified infection, as they should be monitored and followed to dismiss future HCV-related complications, such us liver diseases complications. The identified miRNA signature could be used as biomarker to monitor HCV fingerprint on HCV-exposed patients.

Project description:In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment.To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks.A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10) IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls.The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon-ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500.).

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HCV reinfection incidence among individuals treated for recent infection.

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HCV reinfection incidence among individuals treated for recent infection.

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