title: Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.
abstract: BACKGROUND
  Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus.
  
  
  METHODS
  A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs.
  
  
  RESULTS
  Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C).
  
  
  CONCLUSIONS
  Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.
authors.affiliation: International Laboratory Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Yen T
authors.initials: YT
authors.lastname: Duong
authors.affiliation: The South African DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa; School of Computational and Applied Mathematics, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Reshma
authors.initials: R
authors.lastname: Kassanjee
authors.affiliation: The South African DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: Alex
authors.initials: A
authors.lastname: Welte
authors.affiliation: Epidemiology and Strategic Information Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Meade
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Epidemiology and Strategic Information Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Anindya
authors.initials: A
authors.lastname: De
authors.affiliation: International Laboratory Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Trudy
authors.initials: T
authors.lastname: Dobbs
authors.affiliation: International Laboratory Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: Rottinghaus
authors.affiliation: International Laboratory Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Nkengasong
authors.affiliation: Thailand Ministry of Public Health-US CDC Collaboration, Bangkok, Thailand.
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Curlin
authors.affiliation: Thailand Ministry of Public Health-US CDC Collaboration, Bangkok, Thailand.
authors.forename: Chonticha
authors.initials: C
authors.lastname: Kittinunvorakoon
authors.affiliation: Thailand Ministry of Public Health-US CDC Collaboration, Bangkok, Thailand.
authors.forename: Boonyos
authors.initials: B
authors.lastname: Raengsakulrach
authors.affiliation: Thailand Ministry of Public Health-US CDC Collaboration, Bangkok, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
authors.affiliation: Thailand Ministry of Public Health-US CDC Collaboration, Bangkok, Thailand.
authors.forename: Kachit
authors.initials: K
authors.lastname: Choopanya
authors.affiliation: Thailand Ministry of Public Health-US CDC Collaboration, Bangkok, Thailand.
authors.forename: Suphak
authors.initials: S
authors.lastname: Vanichseni
authors.affiliation: National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Maofeng
authors.initials: M
authors.lastname: Qiu
authors.affiliation: National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Yu
authors.affiliation: National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hao
authors.affiliation: California Department of Public Health, Richmond, California, United States of America.
authors.forename: Neha
authors.initials: N
authors.lastname: Shah
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Hanoi, Vietnam.
authors.forename: Linh-Vi
authors.initials: LV
authors.lastname: Le
authors.affiliation: CDC-Kenya, Nairobi, Kenya.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Kim
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
authors.forename: Tuan Anh
authors.initials: TA
authors.lastname: Nguyen
authors.affiliation: Noguchi Memorial Institute for Medical Research, Accra, Ghana.
authors.forename: William
authors.initials: W
authors.lastname: Ampofo
authors.affiliation: International Laboratory Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Bharat S
authors.initials: BS
authors.lastname: Parekh
mesh_terms: D000915:Antibody Affinity; D002138:Calibration; D015488:HIV Antigens / Q000276:immunology; D006679:HIV Seropositivity / Q000175:diagnosis / Q000453:epidemiology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques / Q000592:standards*; D012698:Serologic Tests / Q000592:standards*
chemical_list: D015488:HIV Antigens