The effect of HIV on SARS-CoV-2 transmission and emergence of variants of concern

Project Summary The emergence and spread of SARS-CoV-2 variants of concern is threatening global health and our ability to prevent COVID-19 disease, raising concerns about a potential new wave of the pandemic. HIV may complicate the trajectory of the COVID-19 pandemic and efforts to eradicate the virus. While most people with a competent immune system successfully clear SARS-CoV-2 infection within days, people living with HIV with weakened immunity can carry persistent infection for months. Individuals with immunodeficiency may also have a higher risk of SARS-CoV-2 reinfection that can further extend the duration of infectiousness with high viral load. As a result, chronically infected individuals are potentially contagious for an extended period of time and may sustain transmission in the community. Similar to other viruses, SARS-CoV-2 accumulates mutations over time as it replicates within the host. Therefore, chronic SARS-CoV-2 infection in the context of a weakened immune system may provide the time and the environment needed for the virus to replicate and evolve genetic mutations associated with survival advantages, including increased transmissibility and resistance to COVID-19 vaccines or treatment. The proposed research aims to understand the overall impact of HIV infection on the SARS-CoV-2 viral evolution and transmission dynamics in a setting with high HIV prevalence. We will address current knowledge gaps by integrating SARS-CoV-2 genomic data, patient-level clinical data, and epidemiological data to achieve the following aims: 1) we will determine the effect of HIV infection on the transmission dynamics of COVID-19 and emergence of SARS-CoV-2 variants; and 2) we will determine the effect of HIV-associated immunosuppression on the acquisition of SARS-CoV-2 mutations. For the first Aim, advanced phylodynamic methods will be applied to determine how HIV affects the transmission and viral evolution of SARS-CoV-2 on a population scale, as well as to describe risk factors that drive individual and population-level COVID-19 transmission. For the second Aim, we will recruit and follow a cohort of COVID-19 patients with and without HIV infection to determine the effect of HIV-associated immunosuppression on the rate of emerging SARS-CoV-2 mutations. The proposed research will also utilize active case finding to minimize sampling bias. Findings from this project will inform the development of optimal public health interventions to control the pandemic by disrupting transmission chains and prevent the emergence and spread of alarming variants.