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

描述(由申请者提供)：这是艾滋病毒预防计划的关键时刻。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，男男性行为者(MSM)仍然是感染艾滋病毒风险最大的群体，尽管检测的外显率很高。因此，预防艾滋病毒传播的努力必须增加男男性接触者中艾滋病毒检测的频率，从而缩短感染者不知道自己的状况及其传播潜力的时间间隔。然而，在高发病率人群中增加艾滋病毒检测频率的策略，将矛盾地增加艾滋病毒感染后“窗口期”的假阴性检测结果的比率，要求在早期感染时使用灵敏度最高的抗体检测或同时进行核酸扩增检测(NAAT)，以进一步缩短窗口期。2003年9月至2008年6月，西雅图和金县公共卫生部门对14005例男男性接触者进行了检测，其中328例(2.3%)HIV抗体阳性，36例(0.3%)抗体阴性的MSM有急性感染。OraQuick Advance快速HIV-1/2抗体检测(OraQuick)只检测到192名感染HIV的男男性接触者中的153人(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的相互作用的理解。在目标1中，我们将评估一种增加艾滋病毒检测频率的干预措施，方法是将艾滋病毒阴性的MSM随机分配到OraQuick进行家庭自我检测，或者在包括NAAT的诊所环境中进行检测。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人的相对能力。在目标#3中，我们将生成数据来评估NAAT在样本(口腔液和干血点)上的性能，这些样本可以作为家庭测试的一部分收集，或者在其他环境中收集，而不需要立即访问NAAT。将进行成本效益分析，以评估每个已确定的艾滋病毒感染病例的不同艾滋病毒检测战略的成本。这项申请涉及为增加预防机会以减少艾滋病毒传播而寻求的几个主题。这些研究主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，以及诊断发展中国家急性和早期感染的方法。如果最近感染艾滋病毒的高感染者得到假阴性的检测结果，并得到不适当的安慰，那么仅将艾滋病毒检测扩大到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：疾控中心最近的建议提倡对所有13-岁的成年人进行普遍的艾滋病毒抗体检测，并对有艾滋病毒感染风险的个人进行更频繁的艾滋病毒检测。然而，在艾滋病毒发病率高的人群中增加艾滋病毒检测频率的战略将矛盾地增加获得艾滋病毒后的“窗口期”的假阴性检测结果的比率，要求在早期感染时使用灵敏度最高的艾滋病毒抗体检测或同时进行核酸扩增检测，以进一步缩短窗口期。这项建议中所述的研究将评估不同的艾滋病毒检测战略，以增加对急性和早期艾滋病毒感染的高传染性个人的诊断，同时增加艾滋病毒感染和传播的高风险人群中艾滋病毒检测的频率。

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.