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

项目总结 尽管在非洲推出了普遍检测和治疗(UTT)，但艾滋病毒发病率仅略有下降，没有 该国正在按部就班地实现联合国艾滋病规划署2030年疫情控制目标。控制努力受到了双方的挑战 “难以接触”的艾滋病毒阳性者仍然是病毒携带者，以及艾滋病毒耐药性(HIVDR)， 促使最近推出多洛替格雷(DTG)。而UTT和DTG可能会导致较低的 尽管存在病毒血症和艾滋病毒/艾滋病，但对其人口层面影响的规模和持久性尚不确定。 乌干达最近的新冠肺炎大流行和社会上的 实施了距离和行动限制，以遏制传播。在这里，我们提出了纵向 病毒载量和流行病学观察(Longview)研究，对COVID影响的前瞻性评估- 19对UTT和DTG方案成果的破坏，包括持久的人口病毒载量抑制， HIVDR和乌干达中南部的艾滋病毒发病率。这项研究将嵌套在Rakai社区内 队列研究(RCCS)，一项以人群为基础的研究，对象为40个艾滋病毒携带者社区中的约20,000人，年龄在15-49岁之间 患病率为9~40%，传播HIVDR~20%。我们建议测量病毒载量和 在七项RCCS调查中对所有HIV血清阳性参与者进行深序列病毒系统发育分析 (每个调查约3,800个艾滋病毒+)，从2013-2025年，跨越2017年的UTT、2019年的DTG和新冠肺炎的引入 在2020年。在目标1中，将在所有研究中为所有艾滋病毒阳性RCC参与者确定约18,500个艾滋病毒病毒载量 来访。基于群体的多轨迹分析将用于评估随时间和深度的病毒载量抑制 来自所有病毒学参与者(1,000个HIV拷贝/毫升)的序列系统发育数据将评估HIVDR。在目标2中， 我们将运用定量和定性的方法来评估新冠肺炎对艾滋病患者求医的影响， 使用率和护理提供情况。具体地说，我们将识别报告中断的艾滋病毒阳性个人 并进行深入访谈，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 新冠肺炎关于提供艾滋病毒护理和治疗的信息。在目标3中，我们将评估艾滋病毒发病率和风险的趋势。 在新冠肺炎出现前后，艾滋病毒在感染和护理连续体中的传播情况。我们会 使用纵向RCCS数据来估计家庭内的艾滋病毒发病率和艾滋病毒传播风险 合伙企业。深序列病毒系统发育数据将用于重建定向传播 并估计在整个护理连续体中传播的可归因率。这项研究将 提供有关新冠肺炎大流行对人群艾滋病毒病毒学和发病率影响的经验数据 在“现实世界”的方案背景下取得的成果。这项研究的首要目标是衡量 新冠肺炎对UTT服务、长期艾滋病毒病毒血症、耐药性和艾滋病毒发病率的影响 非洲的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.