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Robert S. Janssen, MD; Glen A. Satten, PhD; Susan L. Stramer, PhD; Bhupat D. Rawal, PhD; Thomas R. O'Brien, MD, MPH; Barbara J. Weiblen, MS; Frederick M. Hecht, MD; Noreen Jack, MBBS, MPH; Farley R. Cleghorn, MD, MPH; James O. Kahn, MD; Margaret A. Chesney, PhD; Michael P. Busch, MD, PhD

JAMA. 1998;280:42-48.

Context.— 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.

Design.— 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).

Settings and Participants.— 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: 2 717 910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection.

Main Outcome Measure.— Ability to identify early HIV infection.

Results.— Estimated mean time to being 3A11 reactive/3A11-LS nonreactive was 129 days (95% confidence interval [CI], 109-149 days). 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.

From the Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Janssen and Satten); the National Reference Laboratory for Infectious Diseases, American Red Cross, Rockville, Md (Dr Stramer); the Blood Centers of the Pacific, Irwin Center, San Francisco, Calif (Drs Rawal and Busch); the Viral Epidemiology Branch, National Cancer Institute, Rockville, Md (Dr O'Brien); Boston Biomedica, Inc, West Bridgewater, Mass (Ms Weiblen); the Department of Laboratory Medicine (Dr Busch), the AIDS Program (Drs Hecht and Kahn), and the Center for AIDS Prevention Studies (Dr Chesney), University of California, San Francisco; the Medical Research Centre, Port-of-Spain, Trinidad (Dr Jack); and the Institute of Human Virology, University of Maryland School of Medicine, Baltimore (Dr Cleghorn).

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