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 HIV 感染的最初几个月，广泛称为“早期 HIV 感染”，其特点是 病毒载量和每个病毒粒子的感染性增加，导致与病毒相比更高的传播率 随后的慢性感染期模型研究估计了早期感染期间的传播。 不成比例地导致人口层面的艾滋病毒发病率：我们团队的成员估计，艾滋病毒 2010 年，感染前 5 个月内的传播占感染事件的 38% 马拉维利隆圭，而 eSwatini 最近的一个模型估计，前三个月的传播 两项研究的结论是，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。 代表早期感染的前几周，其特点是病毒载量和传染性最高。 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 该研究小组的成员表明，性传播感染 (STI) 诊所是 用于 AHI 检测的持续高产量设置以及整合的干预措施 (iKnow - NCT02467439) AHI 筛查、辅助伴侣通知和 STI 诊所的社会接触转介可以有效识别 iKnow 团队汇集了最大的有记录的艾滋病毒感染者群体之一。 2015 年至 2019 年，马拉维利隆圭 Bwaila STI 诊所发生的 AHI（n=115） 使用调查问卷， 家庭 GPS 和 iKnow 研究的系统发育数据，拟议项目将检查预防措施 以 AHI 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，并以地理区域为补充 具体来说，我们将： 1) 调查 与 AHI 相关的人员和地点的特征；2）AHI 病例的时空聚集性测试 并确定时空 AHI 簇是否通过系统发育相关传播形成 3) 模拟针对急性和早期干预措施对艾滋病毒发病率的影响； 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。 在急性和早期艾滋病毒感染期间采取干预措施以支持完成这一工作。 项目和申请人发展成为独立研究者，拟议的培训计划包括 全球系统发育学、系统发育地理学、数学模型和艾滋病毒专家的密切指导 预防，以及外部课程作业和阅读材料，申请人将开展科学交流。 通过手稿撰写和向 PANGEA HIV 联盟的演示来培养技能。