How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH
High levels of reactive oxygen species (ROS) are present in people living with HIV (PLWH), produced by intense physical activity; in response, our body produces antioxidant molecules. ROS influence the expression of gene-encoding enzymes and transporters involved in drug biotransformation. In additi...
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2025-01-01
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| author | Jessica Cusato Anna Mulasso Micol Ferrara Alessandra Manca Guido Accardo Alice Palermiti Miriam Antonucci Gianluca Bianco Francesco Chiara Jacopo Mula Maria Cristina Tettoni Simone Cuomo Giulia Trevisan Stefano Bonora Giovanni Di Perri Corrado Lupo Alberto Rainoldi Antonio D’Avolio |
| author_facet | Jessica Cusato Anna Mulasso Micol Ferrara Alessandra Manca Guido Accardo Alice Palermiti Miriam Antonucci Gianluca Bianco Francesco Chiara Jacopo Mula Maria Cristina Tettoni Simone Cuomo Giulia Trevisan Stefano Bonora Giovanni Di Perri Corrado Lupo Alberto Rainoldi Antonio D’Avolio |
| author_sort | Jessica Cusato |
| collection | DOAJ |
| description | High levels of reactive oxygen species (ROS) are present in people living with HIV (PLWH), produced by intense physical activity; in response, our body produces antioxidant molecules. ROS influence the expression of gene-encoding enzymes and transporters involved in drug biotransformation. In addition, pharmacogenetics can influence transporter activity, and thus drug exposure. Currently, no studies concerning this topic are present in the literature. The aim of this study was to investigate whether some antioxidant molecules, physical exercise, and genetic variants could affect dolutegravir (DTG) concentrations in PLWH, switching from triple to dual therapy. Thirty PLWH were recruited and analyzed at baseline (triple therapy), and 6 months after (dual therapy). Physical capacities were investigated using validated tools. Drug concentrations and oxidative stress biomarkers levels were evaluated through liquid chromatography coupled with tandem mass spectrometry, while genetic variants through real-time PCR. No statistical differences were suggested for drug concentrations, with the exception of intracellular DTG (<i>p</i> = 0.047). Statistically significant correlations between DTG plasma concentrations and white blood cells (<i>p</i> = 0.011; S = 0.480) and cytoplasmic N-acetyl-cysteine (<i>p</i> = 0.033; S = −0.419) were observed. Finally, white blood cells and BMI remained in the final multivariate regression model as predictors of DTG concentrations. This is the first study showing possible factors related to oxidative stress impacting DTG exposure. |
| format | Article |
| id | doaj-art-40688e4e0df2412e8f6956c15b438a01 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-40688e4e0df2412e8f6956c15b438a012025-01-24T13:19:25ZengMDPI AGAntioxidants2076-39212025-01-011418210.3390/antiox14010082How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWHJessica Cusato0Anna Mulasso1Micol Ferrara2Alessandra Manca3Guido Accardo4Alice Palermiti5Miriam Antonucci6Gianluca Bianco7Francesco Chiara8Jacopo Mula9Maria Cristina Tettoni10Simone Cuomo11Giulia Trevisan12Stefano Bonora13Giovanni Di Perri14Corrado Lupo15Alberto Rainoldi16Antonio D’Avolio17Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyNeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, ItalyASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, ItalyLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyUnit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, ItalyLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyLaboratory of Clinical Pharmacology S. Luigi A.O.U., Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole, Orbassano, 10043 Turin, ItalyLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, ItalyNeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, ItalyUnit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyUnit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyUnit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyNeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, ItalyNeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, ItalyLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, ItalyHigh levels of reactive oxygen species (ROS) are present in people living with HIV (PLWH), produced by intense physical activity; in response, our body produces antioxidant molecules. ROS influence the expression of gene-encoding enzymes and transporters involved in drug biotransformation. In addition, pharmacogenetics can influence transporter activity, and thus drug exposure. Currently, no studies concerning this topic are present in the literature. The aim of this study was to investigate whether some antioxidant molecules, physical exercise, and genetic variants could affect dolutegravir (DTG) concentrations in PLWH, switching from triple to dual therapy. Thirty PLWH were recruited and analyzed at baseline (triple therapy), and 6 months after (dual therapy). Physical capacities were investigated using validated tools. Drug concentrations and oxidative stress biomarkers levels were evaluated through liquid chromatography coupled with tandem mass spectrometry, while genetic variants through real-time PCR. No statistical differences were suggested for drug concentrations, with the exception of intracellular DTG (<i>p</i> = 0.047). Statistically significant correlations between DTG plasma concentrations and white blood cells (<i>p</i> = 0.011; S = 0.480) and cytoplasmic N-acetyl-cysteine (<i>p</i> = 0.033; S = −0.419) were observed. Finally, white blood cells and BMI remained in the final multivariate regression model as predictors of DTG concentrations. This is the first study showing possible factors related to oxidative stress impacting DTG exposure.https://www.mdpi.com/2076-3921/14/1/82antioxidantsphysical capacitiesROSHAARTantiretroviral treatment |
| spellingShingle | Jessica Cusato Anna Mulasso Micol Ferrara Alessandra Manca Guido Accardo Alice Palermiti Miriam Antonucci Gianluca Bianco Francesco Chiara Jacopo Mula Maria Cristina Tettoni Simone Cuomo Giulia Trevisan Stefano Bonora Giovanni Di Perri Corrado Lupo Alberto Rainoldi Antonio D’Avolio How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH Antioxidants antioxidants physical capacities ROS HAART antiretroviral treatment |
| title | How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH |
| title_full | How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH |
| title_fullStr | How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH |
| title_full_unstemmed | How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH |
| title_short | How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH |
| title_sort | how antiretroviral drug concentrations could be affected by oxidative stress physical capacities and genetics a focus on dolutegravir treated male plwh |
| topic | antioxidants physical capacities ROS HAART antiretroviral treatment |
| url | https://www.mdpi.com/2076-3921/14/1/82 |
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