Developing a regionally representative risk assessment tool to identify men at highest risk of HIV acquisition in sub-Saharan Africa

项目摘要/摘要 背景：在撒哈拉以南非洲(SSA)，艾滋病毒预防工作落后于联合国艾滋病规划署的目标。大致 每年有730,000名成年人感染，其中男性占新感染人数的三分之一以上。 生物医学艾滋病毒预防战略，如口服和注射暴露前预防(PrEP)，是 减少艾滋病毒感染的有希望的措施。然而，向所有男性提供PrEP是不可行的，而且 没必要。需要风险分层方法来识别感染艾滋病毒风险最高的男性和 最需要的是PrEP。尽管已经为妇女开发了多种风险评估工具，但很少有工具 是为男性设计的。已经开发的那些在内部和外部都有重要限制 外部有效性。这项提案的目标是开发一种风险评估工具，用于识别风险最高的男性 在具有区域代表性的数据集中使用严格的分析方法获取艾滋病毒。 方法和具体目标：在目标1中，我们将使用来自15个SSA国家的具有国家代表性的数据 作为基于人口的艾滋病毒影响评估(PHIA)的一部分，从2015-2019年收集的尼日利亚艾滋病 指标和影响调查(NAIIS)和南非全国艾滋病毒流行、发病率和行为 调查(SABSSM)。这15项调查代表了122名人口中每年新增24.9万名男性感染者 上百万易受影响的男人。这些调查都有一套生物标志物(限制性抗原亲和力酶 免疫分析、HIV-1病毒载量和抗逆转录病毒药物检测)表明最近感染了HIV-1。我们会 应用两种机器学习方法开发风险评估工具，以识别最多15-49岁的男性 感染HIV-1的风险。我们将计算接收器工作特性曲线(AUC)下的面积，以及 在选定阈值下的灵敏度和特异度。在目标2中，我们将在10个第二轮中对工具进行外部验证 2020-2022年在南沙进行的全国调查，并选择最终工具。使用最后一个工具，我们将估计 AUC和有意义阈值下的灵敏度和特异度。在每个阈值上，我们将计算 感染HIV-1风险增加的男性人数，需要接受PrEP治疗以避免出现一个新的 感染人数，以及估计避免的感染人数。 团队：这是一项由多名首席调查员(MPI)领导的提案-一名具有艾滋病毒流行病学专业知识的人 一种是在SSA中进行预防，另一种是使用复杂的调查数据，具有丰富的统计经验。该队 包括在机器学习和生物医学艾滋病毒预防方面具有专业知识的合作调查人员。他们受到支持 由区域艾滋病毒预防专家组成的技术咨询小组；PHIA的主要调查人员， NAIIS和SABSSM调查；以及艾滋病毒研究领域的专家生物统计学家。 影响：我们将使用严格的方法开发一种区域工具，以识别感染艾滋病毒风险最高的男性。 这项研究对于有针对性地应对艾滋病毒并最终结束SSA的艾滋病毒流行至关重要。

PROJECT SUMMARY/ABSTRACT Background: In sub-Saharan Africa (SSA), HIV prevention has lagged behind UNAIDS targets. Approximately 730,000 adults are infected each year, with men accounting for more than one third of these new infections. Biomedical HIV prevention strategies, such as oral and injectable pre-exposure prophylaxis (PrEP), are promising measures for reducing HIV acquisition. However, providing PrEP to all men is infeasible and unnecessary. Risk stratification approaches are needed to identify men at highest risk of HIV acquisition and in greatest need of PrEP. Although multiple risk assessment tools have been developed for women, few tools have been developed for men. Those that have been developed have important limitations with respect to internal and external validity. The goal of this proposal is to develop a risk assessment tool for identifying men at highest risk for HIV acquisition using rigorous analytic methods in a regionally representative dataset. Methods and Specific Aims: In Aim 1, we will use nationally representative data from 15 SSA countries collected from 2015-2019 as part of the Population-based HIV Impact Assessments (PHIAs), the Nigeria AIDS Indicator and Impact Surveys (NAIIS), and the South African National HIV Prevalence, Incidence and Behaviour Survey (SABSSM). These 15 surveys represent 249,000 new annual male infections in a population of 122 million susceptible men. These surveys all have a set of biomarkers (limiting-antigen avidity enzyme immunoassay, HIV-1 viral load, and antiretroviral drug detection) indicative of recent HIV-1 infection. We will apply two machine-learning methods to develop risk assessment tools to identify men aged 15-49 at greatest risk of HIV-1. We will calculate the area under the receiver operating characteristic curve (AUC), as well as sensitivity and specificity at select thresholds. In Aim 2, we will externally validate the tools in ten second-round national surveys conducted in SSA from 2020-2022 and select a final tool. Using the final tool, we will estimate the AUC and the sensitivity and specificity at meaningful thresholds. At each threshold, we will calculate the number of men at increased risk of HIV-1 infection, the number needed to treat with PrEP to avert one new infection, and the estimated number of infections averted. Team: This is a proposal led by multiple Principal Investigators (mPIs)—one with epidemiologic expertise in HIV prevention in SSA and the other with extensive statistical experience using complex survey data. The team includes co-investigators with expertise in machine learning and biomedical HIV prevention. They are supported by a technical advisory panel of regional HIV prevention specialists; the principal investigators of the PHIA, NAIIS, and SABSSM surveys; and an expert biostatistician in the field of HIV research. Impact: We will use rigorous methods to develop a regional tool to identify men at highest risk of HIV acquisition. This research is crucial for a targeted HIV response and ultimately ending the HIV epidemic in SSA.