antibacterial activity of antiretroviral drugs on key commensal bacteria from the human microbiota.

INTRODUCTION

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.

METHODS

We determined the antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains.

RESULTS

Our results demonstrate that 5 antiretroviral drugs have antibacterial activity against gut and vaginal human commensal bacteria. Zidovudine has antibacterial activity against , and , abacavir against , efavirenz against and and bictegravir against spp. and . Moreover, we describe for the first time that elvitegravir has antibacterial activity against and and, most importantly, against vancomycin-resistant spp. and methicillin-resistant strains with MIC values of 4-16 and 4 µg/mL, respectively showing high level of effectiveness against the tested multidrug-resistant bacteria.

DISCUSSION

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.