Epidemiological, Geospatial, and Phylogenetic Evidence to Inform Interventions Against HIV Transmission during Acute and Early HIV Infection in Lilongwe, Malawi

项目摘要 艾滋病毒感染的最初几个月，广义上称为“早期艾滋病毒感染”，其特征是升高的 病毒载量和增加的每病毒体感染性，导致更高的传播率相比， 慢性感染期。模拟研究估计，在感染早期， 不成比例地导致人口水平的艾滋病毒发病率：我们的团队成员估计， 2010年，感染头五个月的传播占感染事件的38%， 马拉维的利隆圭，而斯威士兰最近的一个模型估计， 感染占15%。两项研究都得出结论，要结束艾滋病毒的流行， 必须解决早期感染期间的传播问题。血清转化前或“急性”期， 代表早期感染的最初几周，其特征是最高的病毒载量和传染性。 急性HIV感染（AHI）的检测需要RNA或抗原检测，这在许多国家很难实施。 设置.该研究小组的成员表明，性传播感染（STI）诊所是 AHI检测的持续高产设置，以及整合干预措施（iKnow-NCT 02467439） AHI筛查、协助伴侣通知和STI诊所的社会接触转介可以有效地识别 未确诊的艾滋病病例。iKnow团队收集了最大的记录人群之一， 2015年至2019年期间在马拉维利隆圭的Bwaila STI诊所进行的非洲AHI（n=115）。采用问卷调查法， 家庭GPS和iKnow研究的系统发育数据，拟议的项目将研究预防 以艾滋病为重点的干预措施的潜力，这些干预措施以性传播感染诊所为基础，并在地理上得到补充， 和人口统计学指导的社区干预。具体而言，我们将：1）调查 AHI病例的时空聚集性检验 并确定是否时空AHI集群通过遗传连锁传播形成 3）模拟人口水平对艾滋病毒发病率的影响，重点是急性和早期的干预措施。 艾滋病毒感染。这些分析将为艾滋病毒传播动力学提供新的见解，并为艾滋病毒的传播提供信息。 在急性和早期艾滋病毒感染期间采取预防传播措施。为了支持完成这一 项目和申请人的发展成为一个独立的调查员，拟议的培训计划包括 全球遗传学、地理学、数学建模和艾滋病毒专家的密切指导 预防，以及外部课程和阅读。申请人将发展科学交流 通过手稿写作和向PANGEA艾滋病联盟的演讲来提高技能。

PROJECT ABSTRACT The first few months of HIV infection, broadly referred to as “early HIV infection,” are characterized by elevated viral loads and increased per-virion infectivity, resulting in higher transmission rates compared to the subsequent chronic infection period. Modeling studies have estimated that transmission during early infection disproportionately contributes to population-level HIV incidence: members of our team estimated that HIV transmission during the first five months of infection accounted for 38% of incident infections in 2010 in Lilongwe, Malawi, while a recent model from eSwatini estimated that transmission during the first three months of infection accounted for 15% of incident infections. Both studies concluded that to end the HIV epidemic, transmission during early infection must be addressed. The pre-seroconversion or “acute” phase, which represents the first several weeks of early infection, is characterized by the highest viral loads and infectivity. Detection of acute HIV infection (AHI) requires RNA or antigen testing, which is difficult to implement in many settings. Members of this study team have shown that sexually transmitted infections (STI) clinics are consistently high-yield settings for AHI detection and that an intervention (iKnow - NCT02467439) integrating AHI screening, assisted partner notification, and social contact referral in STI clinics can efficiently identify undiagnosed cases of HIV. The iKnow team assembled one of the largest documented cohorts of persons with AHI in Africa (n=115) between 2015 and 2019 at Bwaila STI clinic in Lilongwe, Malawi. Using questionnaire, household GPS, and phylogenetic data from the iKnow study, the proposed project will examine the prevention potential of AHI-focused interventions that are anchored in STI clinics and supplemented by geographically- and demographically-guided interventions in communities. Specifically, we will: 1) investigate the characteristics of persons and places associated with AHI; 2) test for spatiotemporal clustering of AHI cases and determine whether spatiotemporal AHI clusters were formed through phylogenetically linked transmission events; and 3) model the population-level impact on HIV incidence of interventions focusing on acute and early HIV infection. These analyses will provide novel insights into HIV transmission dynamics and inform interventions against transmission during acute and early HIV infection. To support the completion of this project and the applicant’s development into an independent investigator, the proposed training plan includes close mentorship by global experts in phylogenetics, phylogeography, mathematical modeling, and HIV prevention, as well as external coursework and readings. The applicant will develop scientific communication skills through manuscript writing and presentations to the PANGEA HIV consortium.