HCV avidity as a tool for detection of recent HCV infection: sensitivity depends on HCV genotype

Samantha J. Shepherd, Scott A. McDonald, Norah E. Palmateer, Rory N. Gunson, Celia Aitken, Gregory J. Dore, David J. Goldberg, Tanya L. Applegate, Andrew R. Lloyd, Behzad Hajarizadeh, Jason Grebely, Sharon J. Hutchinson

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Abstract

Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously-developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as =250 IU/ml). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR=0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (=52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognised.
Original languageEnglish
Pages (from-to)120-130
Number of pages10
JournalJournal of Medical Virology
Volume90
Issue number1
Early online date18 Sep 2017
DOIs
Publication statusPublished - Jan 2018

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Virus Diseases
Hepacivirus
Genotype
Infection
Odds Ratio
Viremia
Chronic Hepatitis C
Public Health
Logistic Models
Demography
Sensitivity and Specificity
Incidence

Keywords

  • Hepatitis C
  • recent infection
  • avidity assay
  • genotype
  • Australia

Cite this

Shepherd, Samantha J. ; McDonald, Scott A. ; Palmateer, Norah E. ; Gunson, Rory N. ; Aitken, Celia ; Dore, Gregory J. ; Goldberg, David J. ; Applegate, Tanya L. ; Lloyd, Andrew R. ; Hajarizadeh, Behzad ; Grebely, Jason ; Hutchinson, Sharon J. / HCV avidity as a tool for detection of recent HCV infection: sensitivity depends on HCV genotype. In: Journal of Medical Virology. 2018 ; Vol. 90, No. 1. pp. 120-130.
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abstract = "Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously-developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as =250 IU/ml). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30{\%}) decreased with infection duration (odds ratio [OR] per week of 0.93; 95{\%} CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR=0.14; 95{\%} CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20{\%}) was estimated at 48{\%} (95{\%} CI:39-56{\%}), 36{\%} (95{\%} CI:20-52{\%}), and 65{\%} (95{\%} CI:54-75{\%}) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (=52 weeks infection duration, all genotypes) was 96{\%} (95{\%} CI:90-98{\%}). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognised.",
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HCV avidity as a tool for detection of recent HCV infection: sensitivity depends on HCV genotype. / Shepherd, Samantha J.; McDonald, Scott A.; Palmateer, Norah E.; Gunson, Rory N.; Aitken, Celia; Dore, Gregory J.; Goldberg, David J.; Applegate, Tanya L.; Lloyd, Andrew R.; Hajarizadeh, Behzad ; Grebely, Jason; Hutchinson, Sharon J.

In: Journal of Medical Virology, Vol. 90, No. 1, 01.2018, p. 120-130.

Research output: Contribution to journalArticle

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T1 - HCV avidity as a tool for detection of recent HCV infection: sensitivity depends on HCV genotype

AU - Shepherd, Samantha J.

AU - McDonald, Scott A.

AU - Palmateer, Norah E.

AU - Gunson, Rory N.

AU - Aitken, Celia

AU - Dore, Gregory J.

AU - Goldberg, David J.

AU - Applegate, Tanya L.

AU - Lloyd, Andrew R.

AU - Hajarizadeh, Behzad

AU - Grebely, Jason

AU - Hutchinson, Sharon J.

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N2 - Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously-developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as =250 IU/ml). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR=0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (=52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognised.

AB - Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously-developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as =250 IU/ml). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR=0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (=52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognised.

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KW - recent infection

KW - avidity assay

KW - genotype

KW - Australia

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