title: Improved testing of recent HIV-1 infections with the BioRad avidity assay compared to the limiting antigen avidity assay and BED Capture enzyme immunoassay: evaluation using reference sample panels from the German Seroconverter Cohort.
abstract: BACKGROUND
  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 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).
  
  
  METHODS
  The 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)].
  
  
  RESULTS
  For 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hauser
authors.affiliation: Division of HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Santos-Hoevener
authors.affiliation: Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Meixenberger
authors.affiliation: Division of HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Sybille
authors.initials: S
authors.lastname: Somogyi
authors.affiliation: Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fiedler
authors.affiliation: Division of HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: Division of HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartmeyer
authors.affiliation: Division of HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jansen
authors.affiliation: Division of HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
authors.forename: Osamah
authors.initials: O
authors.lastname: Hamouda
authors.affiliation: Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Bannert
authors.affiliation: Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuecherer
mesh_terms: D000915:Antibody Affinity / Q000276:immunology*; D015331:Cohort Studies; D005858:Germany; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D006679:HIV Seropositivity / Q000175:diagnosis* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods* / Q000592:standards*; D011933:Reagent Kits, Diagnostic; D012015:Reference Standards
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D011933:Reagent Kits, Diagnostic