title: Evaluation of a multiplex assay for estimation of HIV-1 incidence.
abstract: OBJECTIVE
  Accurate methods of estimating HIV-1 incidence are critical for monitoring the status of the epidemic and the impact of prevention strategies. Although several laboratory-based tests have been developed strictly for this purpose, several limitations exist and improved methods or technologies are needed. We sought to further optimize a previously described bead-based, HIV-1-specific multiplex assay with the capability of measuring multiple immune responses for determining recent infection.
  
  
  METHODS
  We refined the customized HIV-1 Bio-Plex assay by determining cutoffs and mean durations of recency (MDR), based on the reactivity to longitudinal seroconversion specimens (n = 1347) from 311 ART-naïve, HIV-1-infected subjects. False-recent rates (FRRs) were calculated for various long-term cohorts, including AIDS patients, individuals on ART, and subtype C specimens. Incidence was estimated for each individual assay analyte from a simulated population with a known incidence of 1%. For improved incidence estimates, multi-analyte algorithms based on combinations of 3 to 6 analytes were evaluated and compared to the performance of each individual analyte.
  
  
  RESULTS
  The MDR for the six analytes varied from 164.2 to 279.4 days, while the multi-analyte algorithm MDRs were less variable with a minimum and maximum value of 228.4 and 277.9 days, respectively. The FRRs for the 7 multi-analyte algorithms evaluated in this study varied from 0.3% to 3.1%, in a population of ART-naïve, long-term individuals. All algorithms yielded improved incidence estimates as compared to the individual analytes, predicting an incidence of 0.95% to 1.02%.
  
  
  CONCLUSIONS
  The HIV-specific multiplex assay described here measures several distinct immune responses in a single assay, allowing for the consideration of multi-analyte algorithms for improved HIV incidence estimates.
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. czv2@cdc.gov
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Curtis
authors.forename: Debra L
authors.initials: DL
authors.lastname: Hanson
authors.forename: M Susan
authors.initials: MS
authors.lastname: Kennedy
authors.forename: S Michele
authors.initials: SM
authors.lastname: Owen
mesh_terms: D000465:Algorithms; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology*; D015497:HIV-1; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D060885:Multiplex Polymerase Chain Reaction; D014481:United States / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents