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

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.