NEW TESTING STRATEGY TO DETECT EARLY HIV-1 INFECTION FOR USE IN INCIDENCE ESTIMATES AND FOR CLINICAL AND PREVENTION PURPOSES

Context.-Differentiating individuals with early human immunodeficiency virus 1 (HIV-1) infection from those infected for longer periods is d ifficult but important for estimating HIV incidence and for purposes o f clinical care and prevention. Objective.-To develop and validate a s erologic testing algorithm in which HIV-1-positive persons with reacti ve test results on a sensitive HIV-1 enzyme immunoassay (EIA) but nonr eactive results on a less sensitive (LS) EIA are identified as having early infection. Design.-Diagnostic test and testing strategy developm ent, validation, and application. Specimens were tested with both a se nsitive HIV-1 EIA (3A11 assay) and a less sensitive modification of th e same EIA (3A11-LS assay). Settings and Participants.-For assay devel opment: 104 persons seroconverting to HIV-1 comprising 38 plasma donor s, 18 patients of a sexually transmitted disease clinic in Trinidad, a nd 48 participants in the San Francisco Men's Health Study (SFMHS); 26 8 men without the acquired immunodeficiency syndrome (AIDS) in the SFM HS 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 f rom 1985 through 1990 and 1 275 449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidenc e estimates: 2 717 910 first-time blood donors. We retrospectively ide ntified persons eligible for a study of early infection. Main Outcome Measure.-Ability to identify early HIV infection. Results.-Estimated m ean time to being 3A11 reactive/3A11-LS nonreactive was 129 days (95% confidence interval [CI], 109-149 days). Our testing strategy accurate ly diagnosed 95% of persons with early infection; however, 0.4% (1/268 ) of men with established infection and 2% (5/207) of persons with lat e-stage AIDS were misdiagnosed as having early HIV-1 infection. Averag e yearly incidence estimates in SFMHS subjects were 1.5% per year vs o bserved average incidence of 1.4 per 100 person-years. Incidence in re peat blood donors using the sensitive/less sensitive assay testing str ategy was 2.95 per 100 000 per year (95% CI, 1.14-6.53/ 100 000) vs ob served incidence of 2.60 per 100 000 person-years (95% CI, 1.49-4.21/1 00 000). Overall incidence in first-time blood donors was 7.18 per 100 000 per year (95% CI, 4.51-11.20/100 000) and did not change statisti cally significantly between 1993 and 1996. Use of the sensitive/less s ensitive testing strategy alone would have identified all 17 persons w ith antibodies to HIV-1 eligible for a study of early HIV-1 infection and would have increased enrollment. Conclusions.-The sensitive/less s ensitive testing strategy provides accurate diagnosis of early HIV-1 i nfection, provides accurate estimates of HIV-1 incidence, can facilita te clinical studies of early HIV-1 infection, and provides information on HIV-1 infection duration for care planning.