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 艾滋病毒感染的前几个月，被广泛称为“早期艾滋病毒感染”，其特征是升高 病毒载荷和每视频感染增加，与 随后的慢性感染期。建模研究估计，早期感染期间的传播 不成比例地为人口级的艾滋病毒事件做出贡献：我们团队的成员估计艾滋病毒 感染的前五个月传播占2010年事件感染的38％ 马拉维的莉隆威，而埃斯瓦蒂尼（Eswatini）的最新模型估计，在头三个月内传播 感染占事件感染的15％。两项研究得出结论，要结束HIV流行， 必须解决早期感染期间的传播。前转换或“急性”阶段，该阶段 代表早期感染的前几周，其特征是病毒载量最高和感染。 检测急性HIV感染（AHI）需要RNA或抗原测试，这在许多人中很难实施 设置。该研究团队的成员表明，性传播感染（STI）诊所是 始终进行AHI检测的高收益设置，并进行干预（IKNOK -NCT02467439）集成 AHI筛查，辅助合作伙伴通知和STI诊所的社交联系转诊可以有效地识别 未诊断的艾滋病毒病例。 IKNOW团队组装了最大的有记录的人群之一 AHI在2015年至2019年之间在非洲（n = 115）在马拉维利隆威的Bwaila STI诊所举行。使用问卷， 家用GPS和IK Knower研究的系统发育数据，拟议的项目将检查预防 以AHI为中心的干预措施的潜力，该干预措施锚定在STI诊所中，并在地理上补充 以及社区中人口统计学的干预措施。具体来说，我们将：1）调查 与AHI相关的人和地方的特征； 2）测试AHI病例的时空聚类 并确定是否通过系统发育的透射形成时空AHI簇 事件； 3）建模人口水平对关注急性和早期的艾滋病毒事件的影响 艾滋病毒感染。这些分析将为HIV传播动态提供新的见解并告知 急性和早期HIV感染期间针对传播的干预措施。支持完成 项目和申请人开发为独立调查员，拟议的培训计划包括 全球系统发育，植物地理学，数学建模和艾滋病毒的密切精神 预防以及外部课程和阅读。该应用程序将发展科学沟通 通过手稿写作和向Pangea HIV财团进行演示的技能。