Understanding Pandemic Evolution through Networked Data (UPEND)

PROJECT SUMMARY/ABSTRACT There are nearly 38 million people living with HIV (PLWH) worldwide who may be vulnerable to poor neurobehavioral and HIV-related outcomes from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our overarching goal is to improve mental health and other clinical outcomes for PLWH during the COVID-19 pandemic. The objective of the proposed research is to explain how COVID- 19 contributes to adverse neurobehavioral and HIV-related outcomes in PLWH and to measure the effectiveness of vaccination as a biologic tool to mitigate COVID-19-associated neurocognitive impairment. This will help us to improve clinical outcomes during this pandemic and inform strategies to better prepare for future disease outbreaks. We will leverage four HIV-focused cohort studies spanning the United States, Thailand, Kenya, Uganda, Tanzania, and Nigeria with approximately 6800 participants before the pandemic and ongoing follow-up of an additional 1000 participants in the COVID-19 era. Aided by similarities across protocols, deidentified data and specimens will be used to achieve the following specific aims: (1) Identify predictors of COVID-19 vaccine uptake and responsiveness in people with and without HIV; (2) Identify clusters of determinants that impacted viral suppression and neurobehavioral health (depression and cognition) among people with HIV during the COVID-19 pandemic; and (3) Determine long term implications of COVID-19 on neurocognition and mortality and the impact of vaccination in mitigating these effects in people with and without HIV. Data will undergo extensive preparation and harmonization to enable the use of advanced statistical methods, including machine-learning approaches, to better understand the complex factors contributing to each outcome of interest, including biologic, social, behavioral, and regional factors. We will systematically capture availability and receipt of COVID-19 vaccinations; identify factors associated with vaccine uptake; use a centralized laboratory to monitor for incident infections (including breakthrough) and immune responses to vaccination; and prospectively survey participants about knowledge, attitudes, and practices related to vaccination to better define specific barriers. Throughout the constantly evolving COVID-19 pandemic, we will evaluate changes in neurocognitive health, HIV viral load, and CD4 count. Participants with and without a history of COVID-19, with and without COVID-19 vaccination, and with and without HIV will be monitored for the development or progression of noninfectious comorbid conditions with a focus on mental health and neurocognitive impairment for up to three years after infection. This research will enable us to draw globally-relevant conclusions about the impact of COVID-19 on HIV care engagement and outcomes, extract lessons for public health responses to COVID-19 and future pandemics, and evaluate the effects of HIV status and vaccination on SARS-CoV-2 outcomes.