AUTHOR=Rubio-Garcia Elisa , Ferrando Núria , Martin Núria , Ballesté-Delpierre Clara , Miró Jose M. , Paredes Roger , Casals-Pascual Climent , Vila Jordi 

TITLE=In vitro antibacterial activity of antiretroviral drugs on key commensal bacteria from the human microbiota

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1306430

DOI=10.3389/fcimb.2023.1306430

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>Antiretroviral therapy has improved life expectancy in HIV-infected patients. However, people living with HIV under antiretroviral therapy are at higher risks of developing chronic complications and acquiring multidrug resistant bacteria than healthy population. These factors have been associated with shifts in gut microbiome composition and immune activation.  It is unclear how antiretroviral drugs affect gut microbiota composition, but it has been observed that antiretroviral treatment is not able to fully restore gut health after HIV infection. Additionally, some antiretroviral drugs have shown antibacterial activity suggesting that these drugs could have a direct impact on the human microbiome composition. </p></sec><sec><title>Methods</title><p>We determined the <italic>in vitro</italic> antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains. </p></sec><sec><title>Results</title><p>Our results demonstrate that 5 antiretroviral drugs have <italic>in vitro</italic> antibacterial activity against gut and vaginal human commensal bacteria. Zidovudine has antibacterial activity against <italic>Escherichia coli</italic>, <italic>Klebsiella pneumoniae</italic> and <italic>Prevotella bivia</italic>, abacavir against <italic>Gardnerella vaginalis</italic>, efavirenz against <italic>G. vaginalis</italic> and <italic>P. bivia</italic> and bictegravir against <italic>Enterococcus</italic> spp. and <italic>G. vaginalis</italic>. Moreover, we describe for the first time that elvitegravir has antibacterial activity against <italic>G. vaginalis</italic> and <italic>P. bivia</italic> and, most importantly, against vancomycin-resistant <italic>Enterococcus</italic> spp. and methicillin-resistant <italic>Staphylococcus aureus</italic> strains with MIC values of 4-16 and 4 µg/mL, respectively showing high level of effectiveness against the tested multidrug-resistant bacteria.</p></sec><sec><title>Discussion</title><p>Our results underscore that some antiretroviral drugs may influence the human microbiota composition. In addition, we report the potential use of elvitegravir to treat multidrug-resistant Gram-positive bacteria warranting the need of clinical studies to repurpose this antiretroviral drug. </p></sec>