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Article

Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV

by
Sergio Barroso
1,2,3,
Mariona Guitart-Mampel
1,2,3,
Francesc Josep García-García
1,2,3,
Judith Cantó-Santos
1,2,3,
Laura Valls-Roca
1,2,3,
Félix Andújar-Sánchez
1,2,3,
Adrià Vilaseca-Capel
1,2,3,
Ester Tobías
1,2,3,
Angela Arias-Dimas
4,
Tania Quesada-López
5,6,
Rafael Artuch
3,4,
Francesc Villarroya
5,6,
Marta Giralt
5,6,
Esteban Martínez
7,8,
Ester Lozano
9,* and
Glòria Garrabou
1,2,3,*
1
Inherited Metabolic Diseases and Muscular Disorders Research Lab, Cellex-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Sciences, University of Barcelona (UB), 08036 Barcelona, Spain
2
Department of Internal Medicine, Hospital Clinic of Barcelona, 08036 Barcelona, Spain
3
CIBERER-Spanish Biomedical Research Centre in Rare Diseases, Carlos III Health Institute, 28029 Madrid, Spain
4
Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
5
Biochemistry and Molecular Biomedicine Department, Biomedicine Institute (IBUB), University of Barcelona (UB), 08014 Barcelona, Spain
6
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain
7
Infectious Diseases Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain
8
CIBER of Infectious Diseases (CIBERINFEC), Carlos III Health Institute, 28029 Madrid, Spain
9
Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona (UB), 08028 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(15), 8418; https://doi.org/10.3390/ijms25158418
Submission received: 23 May 2024 / Revised: 20 July 2024 / Accepted: 25 July 2024 / Published: 1 August 2024
(This article belongs to the Section Molecular Immunology)
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Abstract

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.
Keywords: antiretroviral treatment; HIV; metabolic profile; mitochondrial toxicity; mitochondrial DNA; inflammatory effects; tenofovir; emtricitabine; efavirenz antiretroviral treatment; HIV; metabolic profile; mitochondrial toxicity; mitochondrial DNA; inflammatory effects; tenofovir; emtricitabine; efavirenz

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MDPI and ACS Style

Barroso, S.; Guitart-Mampel, M.; García-García, F.J.; Cantó-Santos, J.; Valls-Roca, L.; Andújar-Sánchez, F.; Vilaseca-Capel, A.; Tobías, E.; Arias-Dimas, A.; Quesada-López, T.; et al. Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV. Int. J. Mol. Sci. 2024, 25, 8418. https://doi.org/10.3390/ijms25158418

AMA Style

Barroso S, Guitart-Mampel M, García-García FJ, Cantó-Santos J, Valls-Roca L, Andújar-Sánchez F, Vilaseca-Capel A, Tobías E, Arias-Dimas A, Quesada-López T, et al. Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV. International Journal of Molecular Sciences. 2024; 25(15):8418. https://doi.org/10.3390/ijms25158418

Chicago/Turabian Style

Barroso, Sergio, Mariona Guitart-Mampel, Francesc Josep García-García, Judith Cantó-Santos, Laura Valls-Roca, Félix Andújar-Sánchez, Adrià Vilaseca-Capel, Ester Tobías, Angela Arias-Dimas, Tania Quesada-López, and et al. 2024. "Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV" International Journal of Molecular Sciences 25, no. 15: 8418. https://doi.org/10.3390/ijms25158418

APA Style

Barroso, S., Guitart-Mampel, M., García-García, F. J., Cantó-Santos, J., Valls-Roca, L., Andújar-Sánchez, F., Vilaseca-Capel, A., Tobías, E., Arias-Dimas, A., Quesada-López, T., Artuch, R., Villarroya, F., Giralt, M., Martínez, E., Lozano, E., & Garrabou, G. (2024). Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV. International Journal of Molecular Sciences, 25(15), 8418. https://doi.org/10.3390/ijms25158418

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