New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes
New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes
复制标题
DOI：
10.1001/jama.280.1.42
复制
发表时间：
1998-07-01
影响因子：
120.7
通讯作者：
Busch, MP
中科院分区：
文献类型：
--
作者：
Janssen, RS;Satten, GA;Busch, MP
背景。-区分早期人类免疫缺陷病毒1（HIV-1）感染者与长期感染者是困难的，但对于估计HIV发病率以及临床护理和预防目的是重要的。为了开发和验证血清学检测算法，其中HIV-1阳性者在敏感的HIV-1酶免疫测定（EIA）上具有反应性检测结果，但在不太敏感的（LS）EIA上具有非反应性结果，被确定为具有早期感染。诊断测试和测试策略的开发、验证和应用。标本进行了测试与敏感的HIV-1 EIA（3A 11检测）和敏感性较低的修改相同的EIA（3A 11-LS检测）。设置和参与者。对于试验开发：104名血清转化为HIV-1的患者，包括38名血浆捐献者、18名特立尼达性传播疾病诊所的患者和48名弗朗西斯科男性健康研究（SFMHS）的参与者; SFMHS中268名感染至少2.5年的非获得性免疫缺陷综合征（AIDS）男性; 207名临床AIDS患者;用于测试策略验证：从1985年到1990年，SFMHS中有488名男性，从1993年到1995年，3个美国红十字会血液中心有1275449名重复献血者; HIV-1发病率估计：2717910名首次献血者。我们回顾性地确定了符合早期感染研究条件的人。能够识别早期艾滋病毒感染。估计至3A 11反应性/3A 11-LS非反应性的平均时间为129天（95%置信区间[CI]，109-149天）。我们的检测策略准确地诊断了95%的早期感染者;然而，0.4%（1/268）的男性感染者和2%（5/207）的晚期艾滋病患者被误诊为早期HIV-1感染。SFMHS受试者的平均年发病率估计值为每年1.5%，而观察到的平均发病率为1.4/100人-年。使用灵敏度/较低灵敏度检测策略的重复献血者的发生率为2.95/100 000/年（95% CI，1.14-6.53/ 100 000），而观察到的发生率为2.60/100 000人-年（95% CI，1.49-4.21/100 000）。首次献血者的总体发病率为每年7.18/100 000（95% CI，4.51-11.20/100 000），1993年至1996年之间无统计学显著性变化。仅使用敏感/不太敏感的检测策略就可以确定所有17名有HIV-1抗体的人，这些人有资格进行早期HIV-1感染的研究，并将增加入组人数。敏感/不太敏感的检测策略提供了早期HIV-1感染的准确诊断，提供了HIV-1发病率的准确估计，可以促进早期HIV-1感染的临床研究，并为护理规划提供关于HIV-1感染持续时间的信息。
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 1 275 449 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 100 000 per year (95% CI, 1.14-6.53/ 100 000) vs observed incidence of 2.60 per 100 000 person-years (95% CI, 1.49-4.21/100 000). 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 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.