title: Detection of recent HIV-1 infection using a new limiting-antigen avidity assay: potential for HIV-1 incidence estimates and avidity maturation studies.
abstract: BACKGROUND
  Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection.
  
  
  METHODS
  We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed.
  
  
  RESULTS
  Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (ω) of 141 days (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar ω in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections.
  
  
  CONCLUSIONS
  These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent ω in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials.
authors.affiliation: Division of Global HIV/AIDS, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Yen T
authors.initials: YT
authors.lastname: Duong
authors.forename: Maofeng
authors.initials: M
authors.lastname: Qiu
authors.forename: Anindya K
authors.initials: AK
authors.lastname: De
authors.forename: Keisha
authors.initials: K
authors.lastname: Jackson
authors.forename: Trudy
authors.initials: T
authors.lastname: Dobbs
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Kim
authors.forename: John N
authors.initials: JN
authors.lastname: Nkengasong
authors.forename: Bharat S
authors.initials: BS
authors.lastname: Parekh
mesh_terms: D000915:Antibody Affinity / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D006679:HIV Seropositivity / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D008137:Longitudinal Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019562:Viral Load
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens