title: Diagnostic performance of line-immunoassay based algorithms for incident HIV-1 infection.
abstract: BACKGROUND
  Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have previously demonstrated that a patient's antibody reaction pattern in a confirmatory line immunoassay (INNO-LIA™ HIV I/II Score) provides information on the duration of infection, which is unaffected by clinical, immunological and viral variables. In this report we have set out to determine the diagnostic performance of Inno-Lia algorithms for identifying incident infections in patients with known duration of infection and evaluated the algorithms in annual cohorts of HIV notifications.
  
  
  METHODS
  Diagnostic sensitivity was determined in 527 treatment-naive patients infected for up to 12 months. Specificity was determined in 740 patients infected for longer than 12 months. Plasma was tested by Inno-Lia and classified as either incident (< = 12 m) or older infection by 26 different algorithms. Incident infection rates (IIR) were calculated based on diagnostic sensitivity and specificity of each algorithm and the rule that the total of incident results is the sum of true-incident and false-incident results, which can be calculated by means of the pre-determined sensitivity and specificity.
  
  
  RESULTS
  The 10 best algorithms had a mean raw sensitivity of 59.4% and a mean specificity of 95.1%. Adjustment for overrepresentation of patients in the first quarter year of infection further reduced the sensitivity. In the preferred model, the mean adjusted sensitivity was 37.4%. Application of the 10 best algorithms to four annual cohorts of HIV-1 notifications totalling 2'595 patients yielded a mean IIR of 0.35 in 2005/6 (baseline) and of 0.45, 0.42 and 0.35 in 2008, 2009 and 2010, respectively. The increase between baseline and 2008 and the ensuing decreases were highly significant. Other adjustment models yielded different absolute IIR, although the relative changes between the cohorts were identical for all models.
  
  
  CONCLUSIONS
  The method can be used for comparing IIR in annual cohorts of HIV notifications. The use of several different algorithms in combination, each with its own sensitivity and specificity to detect incident infection, is advisable as this reduces the impact of individual imperfections stemming primarily from relatively low sensitivities and sampling bias.
authors.affiliation: Swiss National Center for Retroviruses, Institute of Medical Virology, University of Zurich, Switzerland. schupbach.jorg@virology.uzh.ch
authors.forename: Jörg
authors.initials: J
authors.lastname: Schüpbach
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Bisset
authors.forename: Martin D
authors.initials: MD
authors.lastname: Gebhardt
authors.forename: Stephan
authors.initials: S
authors.lastname: Regenass
authors.forename: Philippe
authors.initials: P
authors.lastname: Bürgisser
authors.forename: Meri
authors.initials: M
authors.lastname: Gorgievski
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Corinne
authors.initials: C
authors.lastname: Andreutti
authors.forename: Gladys
authors.initials: G
authors.lastname: Martinetti
authors.forename: Christoph
authors.initials: C
authors.lastname: Niederhauser
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfister
authors.forename: Detlev
authors.initials: D
authors.lastname: Schultze
authors.forename: Marcel
authors.initials: M
authors.lastname: Brandenberger
authors.forename: Franziska
authors.initials: F
authors.lastname: Schöni-Affolter
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000328:Adult; D000465:Algorithms; D019411:Clinical Laboratory Techniques / Q000379:methods*; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000175:diagnosis* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000276:immunology; D012680:Sensitivity and Specificity; D014773:Virology / Q000379:methods*
chemical_list: D015483:HIV Antibodies