Comparisons of Public Health Screening Methods for Acute and Early HIV Infection

描述（由申请人提供）：这是艾滋病预防项目的关键时刻。最近的建议提倡普遍进行艾滋病毒抗体检测，以确定估计有25%的艾滋病毒感染者不知道自己的艾滋病毒状况。在美国，尽管检测的外显率很高，但男男性行为者（MSM）仍然是感染艾滋病毒风险最大的群体。因此，预防艾滋病毒传播的努力必须增加男男性行为者进行艾滋病毒检测的频率，从而缩短感染者不知道其状况和传播可能性的时间间隔。然而，在高发病率人群中增加艾滋病毒检测频率的策略会在艾滋病毒感染后的“窗口期”增加假阴性检测结果的比率，这需要在早期感染时使用灵敏度最高的抗体检测或并发核酸扩增检测（NAAT）来进一步缩短窗口期。2003年9月至2008年6月，西雅图和金县公共卫生部检测的14005份男男性行为者样本中，328名（2.3%）男男性行为者呈艾滋病毒抗体阳性，36名（0.3%）抗体阴性的男男性行为者患有急性感染。OraQuick ADVANCE快速HIV-1/2抗体测试（OraQuick）在通过快速测试筛选的192名感染hiv的男男性行为者中仅检测出153名（80%）。拟议的研究将增加我们对艾滋病毒检测频率，检测敏感性和急性和早期艾滋病毒感染诊断之间相互作用的理解。在目标#1中，我们将评估一种干预措施，通过将HIV阴性的男男性行为者随机分配到使用OraQuick进行家庭自检或在包括NAAT的诊所环境中进行检测来增加HIV检测的频率。在目标#2中，我们将比较三种快速艾滋病毒抗体检测的实时性能，以确定它们在感染艾滋病毒后立即检测出患者的相对能力。在目标#3中，我们将生成数据来评估NAAT对标本（口服液和干血斑）的性能，这些标本可以作为家庭测试的一部分收集，也可以在没有立即获得NAAT的其他环境中收集。将进行成本效益分析，以评估确定的每个艾滋病毒感染病例的不同艾滋病毒检测策略的成本。本申请涉及几个主题，旨在促进预防机会，减少艾滋病毒传播。这些研究课题包括增加对急性和早期艾滋病毒感染的检测的方法，包括快速检测和NAAT的结合，以及在发展中国家诊断急性和早期感染的方法。如果最近感染艾滋病毒的高度传染性患者得到假阴性检测结果，并不适当地放心，扩大艾滋病毒检测，仅进行抗体检测可能会产生不良影响。PHSKC和华盛顿大学之间的跨学科合作将支持这一转化研究，为地方、国家和国际公共卫生政策提供信息。公共卫生相关性：最近的疾病预防控制中心建议提倡对所有13-64岁的成年人进行普遍的艾滋病毒抗体检测，并对有感染艾滋病毒风险的个体进行更频繁的艾滋病毒检测。然而，在艾滋病毒高发病率人群中增加艾滋病毒检测频率的策略会在艾滋病毒感染后的“窗口期”增加假阴性检测结果的比率，这需要在早期感染时使用灵敏度最高的艾滋病毒抗体检测或并发核酸扩增检测（NAAT）来进一步缩短窗口期。本提案中描述的研究将评估不同的艾滋病毒检测策略，以增加对急性和早期艾滋病毒感染的高传染性个体的诊断，同时增加艾滋病毒感染和传播高风险人群的艾滋病毒检测频率。

DESCRIPTION (provided by applicant): This is a critical time for HIV prevention programs. Recent recommendations advocate universal HIV antibody testing in order to identify the estimated 25% of HIV-infected individuals who are unaware of their HIV status. In the United States, men who have sex with men (MSM) still represent the group with the greatest risk for HIV acquisition despite a high penetrance of testing. Efforts to prevent HIV transmission must therefore increase the frequency of HIV testing among MSM and thereby decrease the time interval that infected individuals are unaware of their status and their potential for transmission. However, strategies that increase the frequency of HIV testing in a population with high incidence will paradoxically increase the rate of false-negative test results in the "window period" following HIV acquisition, requiring the use of antibody tests with the highest sensitivity in early infection or concurrent nucleic acid amplification testing (NAAT) to shorten the window period further. Of 14005 specimens from MSM tested by Public Health - Seattle & King County (PHSKC) from September 2003 to June 2008, 328 (2.3%) MSM were HIV antibody-positive, and 36 (0.3%) antibody-negative MSM had acute infection. The OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraQuick) detected only 153 (80%) of the 192 HIV-infected MSM screened by the rapid test. The proposed studies will increase our understanding of the interactions between the frequency of HIV testing, test sensitivity, and the diagnosis of acute and early HIV infection. In Aim #1, we will evaluate an intervention to increase the frequency of HIV testing by randomizing HIV-negative MSM to either home self-testing with OraQuick or to testing in clinic settings that include NAAT. In Aim #2 we will compare the real-time performance of three rapid HIV antibody tests in order to determine their relative capabilities to detect persons immediately after HIV acquisition. In Aim #3, we will generate data to evaluate the performance of NAAT on specimens (oral fluids and dried blood spots) that could be collected as part of home testing or in other settings without immediate access to NAAT. Cost-effectiveness analyses will be performed to evaluate the costs of different HIV testing strategies per case of HIV infection identified. This application addresses several topics that had been sought to advance prevention opportunities to reduce HIV transmission. These research topics include methods to increase the detection of acute and early HIV infection, including the combination of rapid assays and NAAT, and ways to diagnose acute and early infection in developing countries. The expansion of HIV testing with antibody testing alone may have undesired effects if highly-infectious persons with recent HIV infection receive false-negative test results and are inappropriately reassured. The cross-disciplinary collaboration between PHSKC and the University of Washington will support this translational research to inform local, national, and international public health policy. PUBLIC HEALTH RELEVANCE: Recent CDC recommendations advocate universal HIV antibody testing for all adults 13-64 years old and more frequent HIV testing for individuals at risk for HIV acquisition. However, strategies that increase the frequency of HIV testing in a population with high HIV incidence will paradoxically increase the rate of false-negative test results in the "window period" following HIV acquisition, requiring the use of HIV antibody tests with the highest sensitivity in early infection or concurrent nucleic acid amplification testing (NAAT) to shorten the window period further. The studies described in this proposal will evaluate different HIV testing strategies to increase the diagnosis of highly infectious individuals with acute and early HIV infection while increasing the frequency of HIV testing among a population at high risk for HIV acquisition and transmission.