Home Institution: University of Ghana, Accra, Ghana
U.S. Institution: Yale University
Project Title: Impact of antiretroviral therapy on mitochondrial function and mitochondrial DNA
Mitochondrial dysfunction, associated with antiretroviral therapy (ART), cannot be solely attributed to polymerase gamma (pol γ) inhibition since only nucleoside reverse transcriptase inhibitors (NRTIs) are known to inhibit pol γ but other antiretroviral drug classes have been associated with mitochondrial dysfunction. Mutations in both pol γ gene and mitochondrial DNA (mtDNA) may cause mitochondrial dysfunction in ART-experienced HIV-infected patients. Thus, it is imperative to investigate pol γ gene and mtDNA mutations before and during ART to ascertain their roles in ART-related mitochondrial dysfunction.
This study seeks to investigate the effect of ART on host mitochondria genome and function of HIV-infected patients. Specifically to:
1. determine whether polymerase gamma mutations are associated with ART-induced mitochondrial dysfunction
2. assess the effect of ART regimens on mitochondrial function using in vitro mitochondrial biomarkers
3. determine the effect of ART regimens on mitochondrial DNA content and sequence
The study will expand our understanding of the effect of ART on the function and genome of host mitochondria, and the resulting clinical manifestations, to inform better patient management.