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Interferon lambda 3 genotype predicts hepatitis C virus RNA levels in early acute infection among people who inject drugs: the InC(3) study.

ABSTRACT: BACKGROUND AND OBJECTIVES:Hepatitis C virus (HCV) RNA level in acute HCV infection is predictive of spontaneous clearance. This study assessed factors associated with HCV RNA levels during early acute infection among people who inject drugs with well-defined acute HCV infection. STUDY DESIGN:Data were from International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC(3)) Study, an international collaboration of nine prospective cohorts studying acute HCV infection. Individuals with available HCV RNA levels during early acute infection (first two months following infection) were included. The distribution of HCV RNA levels during early acute infection were compared by selected host and virological factors. RESULTS:A total of 195 individuals were included. Median HCV RNA levels were significantly higher among individuals with interferon lambda 3 (IFNL3, formerly called IL28B) CC genotype compared to those with TT/CT genotype (6.28 vs. 5.39logIU/mL, respectively; P=0.01). IFNL3 CC genotype was also associated with top tertile HCV RNA levels (?6.3log IU/mL; vs. TT/CT genotype; adjusted Odds Ratio: 4.28; 95%CI: 2.01, 9.10; P<0.01). CONCLUSIONS:This study indicates that IFNL3 CC genotype predicts higher HCV RNA levels in early acute HCV infection.

SUBMITTER: Hajarizadeh B

PROVIDER: S-EPMC4279031 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Interferon lambda 3 genotype predicts hepatitis C virus RNA levels in early acute infection among people who inject drugs: the InC(3) study.

Hajarizadeh Behzad B Grady Bart B Page Kimberly K Kim Arthur Y AY McGovern Barbara H BH Cox Andrea L AL Rice Thomas M TM Sacks-Davis Rachel R Bruneau Julie J Morris Meghan M Amin Janaki J Schinkel Janke J Applegate Tanya T Maher Lisa L Hellard Margaret M Lloyd Andrew R AR Prins Maria M Geskus Ronald B RB Dore Gregory J GJ Grebely Jason J

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 20140908 3

<h4>Background and objectives</h4>Hepatitis C virus (HCV) RNA level in acute HCV infection is predictive of spontaneous clearance. This study assessed factors associated with HCV RNA levels during early acute infection among people who inject drugs with well-defined acute HCV infection.<h4>Study design</h4>Data were from International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC(3)) Study, an international collaboration of nine prospective cohorts studying acute HCV in ...[more]

PMID: 25256151

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Project description:BackgroundThe aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection.MethodsACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment).ResultsAmong 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8).ConclusionsThis study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy. ACTIVATE trial registration number: NCT01364090 - May 31, 2011.

Project description:ImportanceThe success of direct-acting antiviral therapies for chronic hepatitis C virus (HCV) infection led the World Health Organization to set elimination targets by 2030. For the United States to achieve these benchmarks, public health responses must target high-risk populations, such as people who inject drugs (PWID), a group with high rates of HCV incidence and low rates of treatment uptake.ObjectiveTo evaluate potential improvements in the HCV care cascade among PWID, focusing on improved testing, treatment uptake, and access to harm reduction.Design, setting, and participantsThis decision analytic model used a differential equation-based dynamic transmission model based on data from New Hampshire, an illustrative state with a large number of PWID and limited HCV treatment infrastructure. Surveillance data through 2020 was used for model parameterization, and the final analysis was conducted in May 2021.Main outcomes and measuresModel forecasts of chronic HCV cases and advanced-stage HCV outcomes from 2022 to 2045.ResultsA total of 6 scenarios were tested: (1) the base case, (2) improved harm reduction, (3) improved testing, (4) improved treatment, (5) improved testing and treatment, and (6) improved testing, treatment, and harm reduction. All scenarios with improved testing, treatment uptake, and/or access to harm reduction were associated with decreases in forecasted HCV prevalence and HCV-associated mortality compared with the base case. Improving harm reduction, testing, and treatment individually were forecast to reduce prevalence of HCV in 2045 from 69.7% in the base case to 62.8%, 45.7%, and 35.5%, respectively. Combining treatment and testing improvements was associated with a 2045 prevalence of 0.3%; adding harm reduction improvements was associated with further reductions in prevalence forecasts (to 0.2%), with fewer total treatments (10 960 vs 13 219 from 2022-2045).Conclusions and relevanceIn this modeling study, no single intervention was projected to achieve World Health Organization HCV elimination targets. Scenarios with improvements in both testing and treatment were associated with a prevalence of less than 3% by 2030 and achieved elimination targets. Adding improvements in harm reduction was associated with faster reductions in prevalence and fewer treatments.

Project description:Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.

Dataset Information

Interferon lambda 3 genotype predicts hepatitis C virus RNA levels in early acute infection among people who inject drugs: the InC(3) study.

Publications

Interferon lambda 3 genotype predicts hepatitis C virus RNA levels in early acute infection among people who inject drugs: the InC(3) study.

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