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

Shepherd, Samantha J.; McDonald, Scott; Palmateer, Norah; Gunson, Rory; Dore, Gregory J.; Goldberg, David J.; Applegate, Tanya; Lloyd, Andrew R.; Hajarizadeh, Behzad; Grebely, Jason; Hutchinson, Sharon J.

doi:10.1002/jmv.24919

Cited by 7 publications

(4 citation statements)

References 45 publications

(72 reference statements)

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“…In addition, in this study we defined recent HCV infection using an HCV antibody avidity index <30% and a positive HCV RNA viral load. This definition is not supported by all studies to date[ 56 ], though the implications on our findings are limited given the small number of HCV RNA positive samples found in our study. Lastly, there are limitations inherent to the statistical methodology, with cautious interpretation of findings suggested.…”

Section: Discussioncontrasting

confidence: 72%

“…Diagnosis can also be delayed and problematic, as it can be difficult to distinguish between acute, resolved, and chronic infections when using immunoglobulin M (IgM) anti-HCV testing[ 48 , 49 ].HCV antibody avidity assays are research tools that measure the binding strength of anti-HCV antibodies in infected individuals. These assays can be used in research to distinguish recent infection from chronic and resolved HCV infections[ 48 , 50 – 56 ]. HCV antibody avidity increases gradually over the course of HCV infection: antibodies produced early in infection have weak antigen-binding ability while mature antibodies generated later in infection have strong antigen-binding capacity.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and mapping of hepatitis C infections among men who have sex with men in New York City

et al. 2018

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Emerging sexually transmitted hepatitis C virus (HCV) epidemics among men who have sex with men (MSM) have been reported worldwide, with higher HCV infection rates among those who are HIV-infected. This study aims to determine prevalence of recent and chronic HCV infections among community-recruited MSM in New York City (NYC), map HCV infections by home, social, and sexual neighborhoods, and identify clusters of genetically linked HCV variants using phylogenetic analysis. The NYC M2M study recruited MSM via modified time-space, venue-based sampling and internet/mobile app-based recruitment during 2010–13. Participants completed a Google Earth map on neighborhoods of where they lived, socialized, and had sex in the last 3 months, an ACASI questionnaire, and a sexual network inventory about their sex partners. The men received HIV testing and provided serum samples. Testing on stored serum samples included HCV antibody and RNA viral load, HCV antibody avidity assay (avidity index <30% with positive viral load is considered recently infected), and HCV RNA extraction and amplification to generate a 432 base-pair region of Core/E1 for sequencing and phylogenetic analysis. Historic local controls were included in the phylogenetic analysis. Of 1,028 MSM, 79.7% were HIV-negative and 20.3% HIV-positive. Twenty nine MSM (2.8%) were HCV antibody-positive. MSM who were HCV antibody-positive reported a median of 2 male sex partners in last 3 months, with 6.9% aged 18–24, 17.2% 25–29, 13.8% 30–39, and 62.1% 40 and over. 8.1% of HIV-positive MSM were HCV antibody-positive vs. 1.5% of HIV-negative men (p<0.0001). Of 29 HCV-antibody positive MSM, 12 (41%) were HCV RNA-positive (11 subtype 1a and 1 subtype 1b). Two of 12 HCV RNA-positive participants had low antibody avidity values, suggesting recent HCV infection. HCV antibody seropositivity was significantly associated with older age >40 years, adjusted odds ratio (aOR) 3.56 (95% CI 1.57, 8.08), HIV-positive serostatus, aOR 3.18 (95% CI 1.40, 7.22), any sexually transmitted infection (STI) in the last 3 months, aOR 2.81 (95% CI 1.11, 7.13), and injection drug use (IDU) ever, aOR 4.34 (95% CI 1.69, 11.17). Mapping of HCV infections differed slightly by home, social, and sexual neighborhoods. Based on phylogenetic analysis from 12 HCV RNA-positive samples, no evidence of a clustered HCV epidemic was found. Overall HCV seroprevalence was 2.8% among community-recruited MSM in NYC, with higher prevalence among HIV-positive MSM compared to HIV-negative MSM. Only two participants were found to have recent HCV infection, with no evidence of a clustered HCV epidemic based on phylogenetic analysis. Our results support testing of HCV infection among HIV-negative MSM if they report having a recent STI and IDU in the past rather than universal HCV testing in all HIV-negative MSM.

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Section: Discussioncontrasting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Prevalence and mapping of hepatitis C infections among men who have sex with men in New York City

et al. 2018

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“…This is consistent with the findings of the previous studies which were based on whole blood (serum) analysis (Croom et al, 2006, Tuaillon et al, 2010, Hope et al, 2011, Shepherd et al, 2013. There was a sharp increment in AI value for genotype 1 compared to non-genotype 1 infections and this is consistent with the report of Shepherd et al (Shepherd et al, 2018).…”

Section: Discussion (Part Ii)supporting

confidence: 93%

Comparison of two immunoassays for concurrent detection of HCV antigen and antibodies among HIV/HCV co-infected patients in dried serum/plasma spots

Eshetu

Hauser

Schmidt

et al. 2020

Journal of Virological Methods

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It is impossible not to mention the invaluable contributions and the unlimited professional and personal support that was extended from my advisors, colleagues and family at large throughout the study, without which it would have been difficult to come up with this thesis.First of all, I would like to thank my advisor Prof. Dr. Norbert Bannert for the opportunity to work in his laboratory and for his proper guidance and overall supervision at all times. I also like to express my gratitude to Prof. Dr. Dirk Brockmann for his advice in my Ph.D. project.My gratitude and my humble appreciation also goes to my direct supervisor Dr. Andrea Hauser for her unreserved and constructive professional comments and support during the times of my study at the Robert Koch institute. Moreover, I want to acknowledge Dr. Patrycja Klink for coordinating the project and for sharing her valuable knowledge and experience with me. I also want to thank our collaborators at the Robert Koch Institute: Prof. Dr.

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“…First, the accuracy of Ab avidity-based results for the identification of recent infections is still debatable, as we could not determine the false recent rate (FRR) of HCV infections. It is also possible that different HCV genotypes and the occurrence of HIV co-infections could have skewed our estimation of recent HCV infections in either direction [9, 35]. Moreover, the gold standard approach for measuring incidence (i.e., negative followed by positive test results through a longitudinal follow-up) cannot be used during outbreak situations.…”

Section: Discussionmentioning

confidence: 99%

Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014–2015

Raffi

Nouhin

Zheng

et al. 2017

Clinical Infectious Diseases

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Background In 2014–2015, 242 individuals aged 2–89 were newly HIV-1 diagnosed in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C and B viruses (HCV, HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV, and HBcIgM Ab for HBV. We performed evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed health care practitioner were obtained from 193 cases and 1499 controls during interviews. Results Cases were co-infected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012–July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P=0.04). Fifty-nine (38.6%) of 153 tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed three main clades, one containing 34 subtypes 1b with tMRCA in 2012, and two with 51 subtypes 6e and tMRCAs in 2002–2003. Conclusions Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically-diverse HCV propagation.

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

Cited by 7 publications

References 45 publications

Prevalence and mapping of hepatitis C infections among men who have sex with men in New York City

Prevalence and mapping of hepatitis C infections among men who have sex with men in New York City

Comparison of two immunoassays for concurrent detection of HCV antigen and antibodies among HIV/HCV co-infected patients in dried serum/plasma spots

Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014–2015

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