Abstract

BackgroundThe variety and limitations of current laboratory methods for estimating HIV-incidence has driven attempts to improve and standardize the performance of serological ‘Tests for Recent HIV-Infections’ (TRI). Primary and follow-up HIV-1 positive plasma samples from individuals with well-defined dates of infection collected as part of the German Seroconverter Cohort provided specimens highly suitable for use in comparing the performance of three TRIs: the AWARE™ BED™ EIA HIV-1 Incidence test (BED-CEIA), Genetic systems HIV-1/HIV-2 Plus O EIA antibody avidity-based assay (BioRad Avidity) and Sedia™ HIV-1 LAg Avidity EIA (LAg Avidity).MethodsThe evaluation panel included 180 specimens: 44 from antiretroviral (ARV)-naïve individuals with recently acquired HIV-infection (≤130 days; 25 B and 19 non-B subtypes) and 136 from long-term (>12 months) infected individuals [101 ARV-naïve subtype B, 16 non-B subtypes, 14 ARV-treated individuals, 5 slow progressors (SLP)].ResultsFor long-term infected, ARV-naïve individuals the false recent rates (FRR) of both the BioRad and LAg Avidity assays were 2% (2/101 for subtype B) and 6% (1/16 for subtype ‘non-B’), while the FRR of the BED-CEIA was 7% (7/101 for subtype B) and 25% (4/16 for subtype ‘non-B’) (all p>0.05). Misclassification of ARV-treated individuals and SLP was rare by LAg (1/14, 0/5) and BioRad Avidity assays (2/14, 1/5) but more frequent by BED-CEIA (5/14, 3/5). Among recently-infected individuals (subtype B), 60% (15/25) were correctly classified by BED-CEIA, 88% (22/25) by BioRad Avidity and significantly fewer by LAg (48%, 12/25) compared to BioRad Avidity (p = 0.005) with a higher true-recency rate among non-B infections for all assays.ConclusionsThis study using well-characterized specimens demonstrated lower FRRs for both avidity methods than with the BED-CEIA. For recently infected individuals the BioRad Avidity assay was shown to give the most accurate results.

Highlights

  • Monitoring the HIV-epidemic and identifying populations amongst whom HIV is spreading is critical for public health services, allowing them to identify groups at risk and target preventive interventions effectively

  • Incidence assays differentiate between recently acquired and longterm infections based on i) the increase in antibody titer [7,8,9], ii) the increase in the proportion of HIV-1 specific immunoglobulin G (IgG) antibodies relative to total IgG [10], iii) the increase of antibody avidity [11,12,13,14,15] or iv) a combination of these markers

  • Slow progressors and ARV-treated individuals were all infected with subtype B, no sequence was available for one patient and the subtype remained unknown (Table 1)

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Summary

Introduction

Monitoring the HIV-epidemic and identifying populations amongst whom HIV is spreading is critical for public health services, allowing them to identify groups at risk and target preventive interventions effectively. Incidence assays differentiate between recently acquired and longterm infections based on i) the increase in antibody titer [7,8,9], ii) the increase in the proportion of HIV-1 specific immunoglobulin G (IgG) antibodies relative to total IgG [10], iii) the increase of antibody avidity [11,12,13,14,15] or iv) a combination of these markers [6,16,17,18,19,20]. The variety and limitations of current laboratory methods for estimating HIV-incidence has driven attempts to improve and standardize the performance of serological ‘Tests for Recent HIV-Infections’ (TRI). Primary and follow-up HIV-1 positive plasma samples from individuals with well-defined dates of infection collected as part of the German Seroconverter Cohort provided specimens highly suitable for use in comparing the performance of three TRIs: the AWARETM BEDTM EIA HIV-1 Incidence test (BED-CEIA), Genetic systems HIV-1/HIV-2 Plus O EIA antibody avidity-based assay (BioRad Avidity) and SediaTM HIV-1 LAg Avidity EIA (LAg Avidity)

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