Long-term impact of universal treatment and dolutegravir on population HIV virologic and incidence outcomes in Africa: The LONGVIEW Study

项目摘要 尽管在非洲推出了通用检测和治疗（UTT），但艾滋病毒感染率仅略有下降， 该国有望实现联合国艾滋病规划署2030年的流行病控制目标。控制工作受到两方面的挑战 “难以接触”的艾滋病毒阳性者仍然存在病毒血症以及艾滋病毒耐药性， 促使最近推出的dolutegravir（DTG）。虽然UTT和DTG可能会导致较低水平的 病毒血症和艾滋病毒/艾滋病，其人口影响的程度和持久性尚不确定。 UTT和DTG的供应因乌干达最近的COVID-19大流行而中断， 实施距离和流动限制以遏制传播。在这里，我们建议纵向 病毒载量和流行病学观察（LONGVIEW）研究，对COVID-1影响的前瞻性评估 19对UTT和DTG项目结果的破坏，包括持久的人群病毒载量抑制， 艾滋病毒/艾滋病防治和艾滋病毒发病率在乌干达中南部。本研究将嵌套在Rakai社区内 队列研究（RCCS），一项基于人群的研究，涉及40个艾滋病毒感染社区的约20，000名15-49岁的人群 流行率约为9-40%，传播艾滋病毒/艾滋病的约为20%。我们建议测量病毒载量， 在7次RCCS调查中对所有HIV血清阳性参与者进行深度序列病毒遗传学研究 2013-2025年（每次调查n~3800例HIV+），跨越2017年UTT、2019年DTG和COVID-19的引入 2020年在目标1中，将在所有研究中确定所有HIV阳性RCCS受试者的约18，500例HIV病毒载量 探访将使用基于组的多轨迹分析评估随时间推移的病毒载量抑制情况， 来自所有病毒血症参与者（> 1，000 HIV拷贝/mL）的序列系统发育数据将评估HIVDR。在目标2中， 我们将使用定量和定性方法评估COVID-19对艾滋病毒治疗寻求的影响， 利用和护理提供。具体来说，我们将确定报告中断的艾滋病毒阳性个体， 艾滋病毒护理和进行深入访谈，以评估ART护理中断的程度和性质。我们还将 与艾滋病毒服务提供者进行焦点小组讨论和深入访谈，以评估 COVID-19对提供艾滋病护理和治疗的影响。在目标3中，我们将评估艾滋病毒发病率和风险的趋势 在COVID-19出现之前和之后，艾滋病毒在感染和护理连续体中的传播。我们将 使用纵向RCCS数据估计以家庭为基础的艾滋病毒发病率以及艾滋病毒传播风险 伙伴关系。深度序列病毒系统发育数据将用于重建定向传播 网络，并估计整个护理连续体的传播的可归因部分。本研究将 提供关于COVID-19大流行对人群艾滋病毒学和发病率影响的经验数据 在“现实世界”的方案环境中取得成果。本研究的总体目标是测量 COVID-19对UTT服务、长期HIV病毒血症、耐药性和HIV发病率的影响， 非洲艾滋病毒控制和消除战略。

PROJECT SUMMARY Despite rollout of Universal Test-and-Treat (UTT) in Africa, HIV incidence has declined only modestly with no country on track to meet UNAIDS 2030 targets for epidemic control. Control efforts are challenged by both “hard-to-engage” HIV-positive persons who remain viremic as well as HIV drug resistance (HIVDR) which has prompted the recent rollout of dolutegravir (DTG). While UTT and DTG are likely to result in lower levels of viremia and HIVDR, there is uncertainty about the magnitude and durability of their population-level impact. Provision of UTT and DTG has been disrupted by the recent COVID-19 pandemic in Uganda and the social distancing and mobility restrictions implemented to contain transmission. Here, we propose the Longitudinal Viral Load and Epidemiological Watch (LONGVIEW) Study, a prospective assessment of the impact of COVID- 19 disruption on UTT and DTG programmatic outcomes, including durable population viral load suppression, HIVDR, and HIV incidence in southcentral Uganda. This study will be nested within the Rakai Community Cohort Study (RCCS), a population-based study of ~20,000 persons, aged 15-49, in 40 communities with HIV prevalence ranging from ~9-40% and transmitted HIVDR ~20%. We propose to measure viral loads and perform deep sequence viral phylogenetics on all HIV-seropositive participants over seven RCCS surveys (n~3800 HIV+ per survey) from 2013-2025, spanning introduction of UTT in 2017, DTG in 2019 and COVID-19 in 2020. In Aim 1, ~18,500 HIV viral loads will be determined for all HIV-positive RCCS participants at all study visits. Group-based multi-trajectory analysis will be used to assess viral load suppression over time and deep sequence phylogenetic data from all viremic participants (>1,000 HIV copies/mL) will assess HIVDR. In Aim 2, we will use quantitative and qualitative methods to assess the impact of COVID-19 on HIV treatment seeking, utilization, and care provision. Specifically, we will identify HIV-positive individuals who report interruptions in HIV care and conduct in-depth interviews to assess the extent and nature of ART care disruption. We will also conduct focus group discussions and in-depth interviews with HIV service providers to assess the impact of COVID-19 on provision of HIV care and treatment. In Aim 3, we will evaluate trends in HIV incidence and risk of HIV transmission across the infection and care continuum before and after COVID-19 emergence. We will use longitudinal RCCS data to estimate HIV incidence as well as HIV transmission risk within household-based partnerships. Deep sequence viral phylogenetic data will be used to reconstruct directed transmission networks and estimate the attributable fraction of transmissions across the care continuum. This study will provide empirical data on the impact of the COVID-19 pandemic on population HIV virologic and incidence outcomes in a “real-world” programmatic setting. The overarching goal of this study is to measure the impact of COVID-19 on UTT services, longer-term HIV viremia, drug resistance, and HIV incidence to inform HIV control and elimination strategies in Africa.