Department of Clinical Microbiology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic of Barcelona, Barcelona, Spain.
Molecular Core Facility, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic of Barcelona, Barcelona, Spain.
Front Cell Infect Microbiol. 2024 Jan 8;13:1306430. doi: 10.3389/fcimb.2023.1306430. eCollection 2023.
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.
We determined the antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains.
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.
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.
抗逆转录病毒疗法提高了感染 HIV 患者的预期寿命。然而，接受抗逆转录病毒治疗的 HIV 感染者比健康人群更容易发生慢性并发症和获得多种耐药菌。这些因素与肠道微生物群落组成和免疫激活的变化有关。抗逆转录病毒药物如何影响肠道微生物群落组成尚不清楚，但人们观察到，抗逆转录病毒治疗并不能完全恢复 HIV 感染后的肠道健康。此外，一些抗逆转录病毒药物具有抗菌活性，这表明这些药物可能对人类微生物群落组成有直接影响。
我们测定了 16 种抗逆转录病毒药物对一组关键的临床相关和人类共生细菌菌株的抗菌活性。
我们的结果表明，5 种抗逆转录病毒药物对肠道和阴道人类共生细菌具有抗菌活性。齐多夫定对 、 和 具有抗菌活性，阿巴卡韦对 、依非韦伦对 和 以及比克替拉韦对 spp. 和 具有抗菌活性。此外，我们首次描述了艾维雷韦对 和 以及最重要的是对万古霉素耐药的 spp. 和耐甲氧西林的 菌株具有抗菌活性，MIC 值分别为 4-16 和 4 µg/mL，对测试的多种耐药菌具有高度有效性。
我们的结果强调，一些抗逆转录病毒药物可能会影响人类微生物群落组成。此外，我们报告了艾维雷韦治疗多种耐药革兰阳性菌的潜在用途，这需要进行临床研究以重新利用这种抗逆转录病毒药物。
