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

流行病学、地理空间和系统发育证据为马拉维利隆圭急性和早期艾滋病毒感染期间艾滋病毒传播的干预措施提供信息

• 批准号: 10402160
• 负责人: Griffin Bell
• 金额: $ 3.71万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402160
• 关键词: AIDS prevention; Acute; Address; Africa; Africa South of the Sahara; Behavior; Characteristics; Chronic; Client; Clinic; Communication; Communities; Data; Detection; Development; Epidemic; Epidemiology; Event; Future; Genetic; Geography; HIV; HIV Infections; HIV Seronegativity; Household; Incidence; Individual; Infection; Intervention; Investigation; Link; Malawi; Manuscripts; Mentorship; Modeling; Neighborhoods; Partner Notification; Patients; Persons; Phase; Phylogenetic Analysis; Population; Prevention; Prevention program; Prevention strategy; Questionnaires; RNA; Reading; Research; Research Personnel; Sexual Partners; Sexually Transmitted Diseases; Study models; Testing; Time; Training; Trees; Viral; Viral Load result; Virion; Work; Writing; acute infection; antigen test; base; chronic infection; cohort; combat; demographics; insight; mathematical model; member; novel; prevent; programs; residence; screening; seroconversion; skills; social contact; spatiotemporal; transmission process

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.

项目摘要 艾滋病毒感染的最初几个月，广义上被称为“早期艾滋病毒感染”，其特征是 病毒载量和每病毒粒子传染性增加，导致与 随后的慢性感染期。模拟研究估计在早期感染期间的传播 不成比例地导致人群水平的艾滋病毒发病率：我们团队的成员估计，艾滋病毒 年，感染前五个月的传播占2010年事件感染的38% 马拉维的利隆圭，而埃斯瓦蒂尼最近的一个模型估计，前三个月的传播 感染人数占事件感染人数的15%。这两项研究的结论都是，为了结束艾滋病毒的流行， 必须解决早期感染期间的传播问题。血清转换前或“急性期”， 代表早期感染的最初几周，其特点是病毒载量和传染性最高。 急性艾滋病毒感染(AHI)的检测需要RNA或抗原检测，这在许多情况下很难实现 设置。该研究小组的成员表明，性传播感染(STI)诊所 持续高收益的AHI检测设置和集成的干预(iKnow-NCT02467439) 性传播感染诊所的AHI筛查、辅助合作伙伴通知和社交联系转介可以有效地识别 未确诊的艾滋病毒病例。IKnow团队汇集了有记录的最大的有记录的人群之一 2015年至2019年在马拉维利隆圭的Bwaila STI诊所进行的非洲AHI(n=115)。通过问卷调查， 家庭GPS和来自iKnow研究的系统发育数据，拟议的项目将检查预防 以性传播感染诊所为基础并辅之以地理上的- 以及以人口统计为导向的社区干预措施。具体来说，我们将：1)调查 与AHI相关的人和场所特征；2)AHI病例的时空聚集性检验 并确定时空AHI簇是否通过系统发育连锁传播形成 事件；以及3)以急性和早期为重点的干预措施对人群一级艾滋病毒发病率的影响的模型 艾滋病毒感染。这些分析将为艾滋病毒传播动态提供新的见解并提供信息 在艾滋病毒急性和早期感染期间针对传播的干预措施。以支持完成这一任务 为了将项目和申请者发展成为独立调查员，拟议的培训计划包括 系统发育、系统地理学、数学模型和艾滋病毒方面的全球专家的密切指导 预防，以及外部课程和阅读材料。申请者将发展科学交流 通过撰写手稿和向泛古大陆艾滋病毒联盟进行演示来提高技能。