How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH
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
Affiliations
Jessica Cusato
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Anna Mulasso
NeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Micol Ferrara
ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy
Alessandra Manca
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Guido Accardo
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Alice Palermiti
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Miriam Antonucci
ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy
Gianluca Bianco
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Francesco Chiara
Laboratory of Clinical Pharmacology S. Luigi A.O.U., Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole, Orbassano, 10043 Turin, Italy
Jacopo Mula
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Maria Cristina Tettoni
ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy
Simone Cuomo
NeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Giulia Trevisan
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Stefano Bonora
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Giovanni Di Perri
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Corrado Lupo
NeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Alberto Rainoldi
NeuroMuscular Function|Research Group, School of Exercise and Sport Sciences, SUISM, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Antonio D’Avolio
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
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 (p = 0.047). Statistically significant correlations between DTG plasma concentrations and white blood cells (p = 0.011; S = 0.480) and cytoplasmic N-acetyl-cysteine (p = 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.
