title: New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes.
abstract: BACKGROUND
  Differentiating individuals with early human immunodeficiency virus 1 (HIV-1) infection from those infected for longer periods is difficult but important for estimating HIV incidence and for purposes of clinical care and prevention.
  
  
  OBJECTIVE
  To develop and validate a serologic testing algorithm in which HIV-1-positive persons with reactive test results on a sensitive HIV-1 enzyme immunoassay (EIA) but nonreactive results on a less sensitive (LS) EIA are identified as having early infection.
  
  
  METHODS
  Diagnostic test and testing strategy development, validation, and application. Specimens were tested with both a sensitive HIV-1 EIA (3A11 assay) and a less sensitive modification of the same EIA (3A11-LS assay).
  
  
  METHODS
  For assay development: 104 persons seroconverting to HIV-1 comprising 38 plasma donors, 18 patients of a sexually transmitted disease clinic in Trinidad, and 48 participants in the San Francisco Men's Health Study (SFMHS); 268 men without the acquired immunodeficiency syndrome (AIDS) in the SFMHS who had been infected for at least 2.5 years; and 207 persons with clinical AIDS; for testing strategy validation: 488 men in the SFMHS from 1985 through 1990 and 1275449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence estimates: 2717910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection.
  
  
  METHODS
  Ability to identify early HIV infection.
  
  
  RESULTS
  Estimated mean time from being 3A11 reactive/3A11-LS nonreactive to being 3A11 reactive/3A11-LS reactive was 129 days (95% confidence interval [CI], 109-149 days) [corrected]. Our testing strategy accurately diagnosed 95% of persons with early infection; however, 0.4% (1/268) of men with established infection and 2% (5/207) of persons with late-stage AIDS were misdiagnosed as having early HIV-1 infection. Average yearly incidence estimates in SFMHS subjects were 1.5% per year vs observed average incidence of 1.4 per 100 person-years. Incidence in repeat blood donors using the sensitive/less sensitive assay testing strategy was 2.95 per 100000 per year (95% CI, 1.14-6.53/100000) vs observed incidence of 2.60 per 100000 person-years (95% CI, 1.49-4.21/100000). Overall incidence in first-time blood donors was 7.18 per 100000 per year (95% CI, 4.51-11.20/100000) and did not change statistically significantly between 1993 and 1996. Use of the sensitive/less sensitive testing strategy alone would have identified all 17 persons with antibodies to HIV-1 eligible for a study of early HIV-1 infection and would have increased enrollment.
  
  
  CONCLUSIONS
  The sensitive/less sensitive testing strategy provides accurate diagnosis of early HIV-1 infection, provides accurate estimates of HIV-1 incidence, can facilitate clinical studies of early HIV-1 infection, and provides information on HIV-1 infection duration for care planning.
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. RXJ1@cdc.gov
authors.forename: R S
authors.initials: RS
authors.lastname: Janssen
authors.forename: G A
authors.initials: GA
authors.lastname: Satten
authors.forename: S L
authors.initials: SL
authors.lastname: Stramer
authors.forename: B D
authors.initials: BD
authors.lastname: Rawal
authors.forename: T R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: B J
authors.initials: BJ
authors.lastname: Weiblen
authors.forename: F M
authors.initials: FM
authors.lastname: Hecht
authors.forename: N
authors.initials: N
authors.lastname: Jack
authors.forename: F R
authors.initials: FR
authors.lastname: Cleghorn
authors.forename: J O
authors.initials: JO
authors.lastname: Kahn
authors.forename: M A
authors.initials: MA
authors.lastname: Chesney
authors.forename: M P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D015492:AIDS Serodiagnosis; D000465:Algorithms; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000175:diagnosis* / Q000453:epidemiology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D008297:Male; D008962:Models, Theoretical; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D015483:HIV Antibodies