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Principal Investigator: Chawangwa Modongo
Organization: UNIVERSITY OF CALIFORNIA-IRVINE
Fiscal Year: 2023
Award: $559,720
Funding agency: National Institute of Allergy and Infectious Diseases
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.
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