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To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-na\u00efve 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 (TNF\u03b1, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNF\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms25158418","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:38:20Z","timestamp":1722515900000},"page":"8418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Na\u00efve People with HIV"],"prefix":"10.3390","volume":"25","author":[{"given":"Sergio","family":"Barroso","sequence":"first","affiliation":[{"name":"Inherited Metabolic Diseases and Muscular Disorders Research Lab, Cellex-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Sciences, University of 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Quesada-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biomedicine Department, Biomedicine Institute (IBUB), University of Barcelona (UB), 08014 Barcelona, Spain"},{"name":"CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-9685","authenticated-orcid":false,"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[{"name":"CIBERER-Spanish Biomedical Research Centre in Rare Diseases, Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Department of Clinical Biochemistry, Institut de Recerca Sant Joan de D\u00e9u, Esplugues de Llobregat, 08950 Barcelona, 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Replication","volume":"12","author":"Mateos","year":"2015","journal-title":"Retrovirology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0140-6736(18)31311-4","article-title":"HIV","volume":"392","author":"Ghosn","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Samji, H., Cescon, A., Hogg, R.S., Modur, S.P., Althoff, K.N., Buchacz, K., Burchell, A.N., Cohen, M., Gebo, K.A., and Gill, M.J. (2013). Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081355"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"INSIGHT START Study Group, Lundgren, J.D., Babiker, A.G., Gordin, F., Emery, S., Grund, B., Sharma, S., Avihingsanon, A., Cooper, D.A., and F\u00e4tkenheuer, G. (2015). Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N. Engl. J. Med., 373, 795\u2013807.","DOI":"10.1056\/NEJMoa1506816"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"TEMPRANO ANRS 12136 Study Group, Danel, C., Moh, R., Gabillard, D., Badje, A., Le Carrou, J., Ouassa, T., Ouattara, E., Anzian, A., and Ntakp\u00e9, J.-B. (2015). A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N. Engl. J. Med., 373, 808\u2013822.","DOI":"10.1056\/NEJMoa1507198"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1016\/S0140-6736(19)30418-0","article-title":"Risk of HIV Transmission through Condomless Sex in Serodifferent Gay Couples with the HIV-Positive Partner Taking Suppressive Antiretroviral Therapy (PARTNER): Final Results of a Multicentre, Prospective, Observational Study","volume":"393","author":"Rodger","year":"2019","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S1473-3099(17)30702-8","article-title":"HIV-1 Drug Resistance before Initiation or Re-Initiation of First-Line Antiretroviral Therapy in Low-Income and Middle-Income Countries: A Systematic Review and Meta-Regression Analysis","volume":"18","author":"Gupta","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1177\/0192623313503519","article-title":"HIV Treatment and Associated Mitochondrial Pathology","volume":"42","author":"Gardner","year":"2014","journal-title":"Toxicol. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0149-2918(00)90004-3","article-title":"Pharmacology of Nucleoside and Nucleotide Reverse Transcriptase Inhibitor-Induced Mitochondrial Toxicity","volume":"22","author":"Kakuda","year":"2000","journal-title":"Clin. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2174\/1570162X15666171120110145","article-title":"Nucleotide Reverse Transcriptase Inhibitors: A Thorough Review, Present Status and Future Perspective as HIV Therapeutics","volume":"15","author":"Holec","year":"2018","journal-title":"Curr. HIV Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1177\/135965350501000407","article-title":"Reverse Transcriptase Inhibitors Alter Uncoupling Protein-1 and Mitochondrial Biogenesis in Brown Adipocytes","volume":"10","author":"Yubero","year":"2005","journal-title":"Antivir. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/QAI.0b013e3181bd564c","article-title":"Genetic and Functional Mitochondrial Assessment of HIV-Infected Patients Developing HAART-Related Hyperlactatemia","volume":"52","author":"Garrabou","year":"2009","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s13181-013-0325-8","article-title":"A Review of the Toxicity of HIV Medications","volume":"10","author":"Margolis","year":"2014","journal-title":"J. Med. Toxicol."},{"key":"ref_15","first-page":"392","article-title":"Drug-Induced Lipotoxicity: Lipodystrophy Associated with HIV-1 Infection and Antiretroviral Treatment","volume":"1801","author":"Villarroya","year":"2010","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Biol. Lipids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1128\/AAC.46.3.716-723.2002","article-title":"Assessment of Mitochondrial Toxicity in Human Cells Treated with Tenofovir: Comparison with Other Nucleoside Reverse Transcriptase Inhibitors","volume":"46","author":"Birkus","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nrd1201","article-title":"Mitochondrial Toxicity of NRTI Antiviral Drugs: An Integrated Cellular Perspective","volume":"2","author":"Lewis","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.2174\/138161211796904731","article-title":"Mitochondrial Toxicity in HAART: An Overview of In Vitro Evidence","volume":"17","author":"Apostolova","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1194\/jlr.M200487-JLR200","article-title":"Modulation of the LDL Receptor and LRP Levels by HIV Protease Inhibitors","volume":"44","author":"Tran","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S1567-7249(02)00042-9","article-title":"In Vitro Evidence of Inhibition of Mitochondrial Protease Processing by HIV-1 Protease Inhibitors in Yeast: A Possible Contribution to Lipodystrophy Syndrome","volume":"1","author":"Mukhopadhyay","year":"2002","journal-title":"Mitochondrion"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10565-016-9362-9","article-title":"Depolarization of Mitochondrial Membrane Potential Is the Initial Event in Non-Nucleoside Reverse Transcriptase Inhibitor Efavirenz Induced Cytotoxicity","volume":"33","author":"Ganta","year":"2017","journal-title":"Cell Biol. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1089\/aid.2007.0262","article-title":"Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status","volume":"24","author":"Shikuma","year":"2008","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1093\/jac\/dku262","article-title":"Lack of Mitochondrial Toxicity of Darunavir, Raltegravir and Rilpivirine in Neurons and Hepatocytes: A Comparison with Efavirenz","volume":"69","author":"Polo","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/hep.23647","article-title":"Inhibition of Mitochondrial Function by Efavirenz Increases Lipid Content in Hepatic Cells","volume":"52","author":"Apostolova","year":"2010","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Domingo, P., Gutierrez, M.d.M., Gallego-Escuredo, J.M., Torres, F., Mateo, G.M., Villarroya, J., de los Santos, I., Domingo, J.C., Villarroya, F., and Rio, L.D. (2014). Effects of Switching from Stavudine to Raltegravir on Subcutaneous Adipose Tissue in HIV-Infected Patients with HIV\/HAART-Associated Lipodystrophy Syndrome (HALS). A Clinical and Molecular Study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089088"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/QAI.0000000000002275","article-title":"Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment-Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials","volume":"83","author":"Cahn","year":"2020","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Barroso, S., Mor\u00e9n, C., Gonz\u00e1lez-Segura, \u00c0., Riba, N., Arnaiz, J.A., Manriquez, M., Santana, G., Blanco, J.L., Larousse, M., and Lonc\u00e0, M. (2019). Metabolic, Mitochondrial, Renal and Hepatic Safety of Enfuvirtide and Raltegravir Antiretroviral Administration: Randomized Crossover Clinical Trial in Healthy Volunteers. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216712"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1111\/hiv.13542","article-title":"Major Revision Version 12.0 of the European AIDS Clinical Society Guidelines 2023","volume":"24","author":"Ambrosioni","year":"2023","journal-title":"HIV Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/QAD.0000000000003369","article-title":"Dolutegravir-Containing HIV Therapy Reversibly Alters Mitochondrial Health and Morphology in Cultured Human Fibroblasts and Peripheral Blood Mononuclear Cells","volume":"37","author":"Ajaykumar","year":"2023","journal-title":"AIDS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1093\/infdis\/jiac175","article-title":"Dolutegravir Suppresses Thermogenesis via Disrupting Uncoupling Protein 1 Expression and Mitochondrial Function in Brown\/Beige Adipocytes in Preclinical Models","volume":"226","author":"Jung","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21556660.2022.2149963","article-title":"Treatment and Comorbidity Burden among People Living with HIV: A Review of Systematic Literature Reviews","volume":"12","author":"Taiwo","year":"2023","journal-title":"J. Drug Assess."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"de Waal, R., Cohen, K., and Maartens, G. (2013). Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063623"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Alikhani, A., Morin, H., Matte, S., Alikhani, P., Tremblay, C., and Durand, M. (2019). Association between Lipodystrophy and Length of Exposure to ARTs in Adult HIV-1 Infected Patients in Montreal. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4446-9"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1089\/apc.2013.0310","article-title":"Rilpivirine Versus Efavirenz with Emtricitabine\/Tenofovir Disoproxil Fumarate in Treatment-Na\u00efve HIV-1\u2013Infected Patients with HIV-1 RNA \u2264100,000 Copies\/ML: Week 96 Pooled ECHO\/THRIVE Subanalysis","volume":"28","author":"Behrens","year":"2014","journal-title":"AIDS Patient Care STDS"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.2165\/00003495-200666110-00012","article-title":"Efavirenz\/Emtricitabine\/Tenofovir Disoproxil Fumarate","volume":"66","author":"Frampton","year":"2006","journal-title":"Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Moyle, G.J., Orkin, C., Fisher, M., Dhar, J., Anderson, J., Wilkins, E., Ewan, J., Ebrahimi, R., and Wang, H. (2015). A Randomized Comparative Trial of Continued Abacavir\/Lamivudine plus Efavirenz or Replacement with Efavirenz\/Emtricitabine\/Tenofovir DF in Hypercholesterolemic HIV-1 Infected Individuals. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116297"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2174\/1570162X18666200106150806","article-title":"Vitamin D and Calcium Supplement Attenuate Bone Loss among HIV Infected Patients Receiving Tenofovir Disoproxil Fumarate\/Emtricitabine\/Efavirenz: An Open-Label, Randomized Controlled Trial","volume":"18","author":"Boontanondha","year":"2020","journal-title":"Curr. HIV Res."},{"key":"ref_38","first-page":"135","article-title":"An Update on the Use of Atripla in the Treatment of HIV in the United States","volume":"2","author":"Horberg","year":"2010","journal-title":"HIV AIDS"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/MCO.0b013e32833cc93d","article-title":"Mitochondrial Metabolic Function Assessed in Vivo and in Vitro","volume":"13","author":"Lanza","year":"2010","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1386-6532(01)00195-0","article-title":"Quantification of Mitochondrial DNA in Peripheral Blood Mononuclear Cells and Subcutaneous Fat Using Real-Time Polymerase Chain Reaction","volume":"22","author":"Gahan","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.mito.2011.06.005","article-title":"Increased Plasma Levels of Extracellular Mitochondrial DNA during HIV Infection: A New Role for Mitochondrial Damage-Associated Molecular Patterns during Inflammation","volume":"11","author":"Cossarizza","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1097\/QAD.0b013e3283400088","article-title":"Serum FGF21 Levels Are Elevated in Association with Lipodystrophy, Insulin Resistance and Biomarkers of Liver Injury in HIV-1-Infected Patients","volume":"24","author":"Domingo","year":"2010","journal-title":"AIDS"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/S1474-4422(11)70155-7","article-title":"FGF-21 as a Biomarker for Muscle-Manifesting Mitochondrial Respiratory Chain Deficiencies: A Diagnostic Study","volume":"10","author":"Suomalainen","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nrendo.2016.206","article-title":"A New Frontier in FGF21 Biology","volume":"13","author":"Potthoff","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yubero, D., Allen, G., Artuch, R., and Montero, R. (2017). The Value of Coenzyme Q10 Determination in Mitochondrial Patients. J. Clin. Med., 6.","DOI":"10.3390\/jcm6040037"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7960386","DOI":"10.1155\/2016\/7960386","article-title":"Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress","volume":"2016","author":"Souza","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41419-018-0429-9","article-title":"Differentiation by Nerve Growth Factor (NGF) Involves Mechanisms of Crosstalk between Energy Homeostasis and Mitochondrial Remodeling","volume":"9","author":"Martorana","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/hep.23909","article-title":"Interleukin-6 Is an Important Mediator for Mitochondrial DNA Repair after Alcoholic Liver Injury in Mice","volume":"52","author":"Zhang","year":"2010","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2044-5040-2-14","article-title":"IL-6 Regulation on Skeletal Muscle Mitochondrial Remodeling during Cancer Cachexia in the Apc Min\/+ Mouse","volume":"2","author":"White","year":"2012","journal-title":"Skelet. Muscle"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S0039-6060(99)70241-2","article-title":"The Serum Interleukin 8 Level Reflects Hepatic Mitochondrial Redox State in Hyperthermochemohypoxic Isolated Liver Perfusion with Use of a Venovenous Bypass","volume":"125","author":"Yamada","year":"1999","journal-title":"Surgery"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12967-018-1599-z","article-title":"Cord Blood Leptin and Insulin Levels in Association with Mitochondrial DNA Content","volume":"16","author":"Vriens","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_53","first-page":"224","article-title":"Release of Mitochondrial DNA Correlates with Peak Inflammatory Cytokines in Patients with Acute Myocardial Infarction","volume":"17","author":"Qin","year":"2017","journal-title":"Anatol. J. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.bbabio.2006.05.001","article-title":"Anti-HIV Drugs and the Mitochondria","volume":"1757","author":"Pinti","year":"2006","journal-title":"Biochim. Biophys. Acta BBA-Bioenerg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/infdis\/jiaa635","article-title":"Human Immunodeficiency Virus Type 1 Vpu Inhibitor, BIT225, in Combination with 3-Drug Antiretroviral Therapy: Inflammation and Immune Cell Modulation","volume":"223","author":"Luscombe","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ji, S., Xu, Y., Han, D., Peng, X., Lu, X., Brockmeyer, N.H., and Wu, N. (2019). Changes in Lipid Indices in HIV+ Cases on HAART. Biomed. Res. Int., 2019.","DOI":"10.1155\/2019\/2870647"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.clinbiochem.2012.12.017","article-title":"Lipid Profile Changes by High Activity Anti-Retroviral Therapy","volume":"46","author":"Duro","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jiph.2015.04.020","article-title":"Emtricitabine\/Rilpivirine\/Tenofovir Disoproxil Fumarate for the Treatment of HIV-1 Infection in Adults","volume":"8","author":"Kabbara","year":"2015","journal-title":"J. Infect. Public Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/cid\/ciy540","article-title":"Doravirine\/Lamivudine\/Tenofovir Disoproxil Fumarate Is Non-Inferior to Efavirenz\/Emtricitabine\/Tenofovir Disoproxil Fumarate in Treatment-Naive Adults With Human Immunodeficiency Virus\u20131 Infection: Week 48 Results of the DRIVE-AHEAD Trial","volume":"68","author":"Orkin","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S1201-9712(02)90107-4","article-title":"The Association of Serum Lactate Dehydrogenase Level with Selected Opportunistic Infections and HIV Progression","volume":"6","author":"Butt","year":"2002","journal-title":"Int. J. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.1086\/381444","article-title":"Drug-Induced Liver Injury Associated with Antiretroviral Therapy That Includes HIV-1 Protease Inhibitors","volume":"38","author":"Sulkowski","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_62","first-page":"159","article-title":"Acute Liver Toxicity of Antiretroviral Therapy (HAART) after Liver Transplantation in a Patient with HIV-HCV Coinfection and Associated Hepatocarcinoma (HCC)","volume":"89","author":"Vennarecci","year":"2003","journal-title":"Tumori"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1089-3261(03)00129-6","article-title":"Cholestasis in HIV-Infected Patients","volume":"8","author":"Te","year":"2004","journal-title":"Clin. Liver Dis."},{"key":"ref_64","unstructured":"World Health Organization (2016). Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach, WHO. [2nd ed.]."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"The DAD Study Group (2007). The members of the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group Class of Antiretroviral Drugs and the Risk of Myocardial Infarction. N. Engl. J. Med., 356, 1723\u20131735.","DOI":"10.1056\/NEJMoa062744"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1016\/j.ijid.2008.04.004","article-title":"Changes in Antioxidant Profile among HIV-Infected Individuals on Generic Highly Active Antiretroviral Therapy in Southern India","volume":"12","author":"Sundaram","year":"2008","journal-title":"Int. J. Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Shi, R., Chen, X., Lin, H., Ding, Y., and He, N. (2022). Incidence of Impaired Kidney Function among People with HIV: A Systematic Review and Meta-Analysis. BMC Nephrol., 23.","DOI":"10.1186\/s12882-022-02721-x"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/QAD.0000000000000486","article-title":"Mitochondrial Disturbances in HIV Pregnancies","volume":"29","author":"Garrabou","year":"2015","journal-title":"AIDS"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhao, J., Schank, M., Wang, L., Li, Z., Nguyen, L.N., Dang, X., Cao, D., Khanal, S., Nguyen, L.N.T., and Thakuri, B.K.C. (2021). Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.658420"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1097\/INF.0000000000000894","article-title":"Decreased Mitochondrial Function Among Healthy Infants Exposed to Antiretrovirals During Gestation, Delivery and the Neonatal Period","volume":"34","author":"Rovira","year":"2015","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1177\/135965350801300311","article-title":"Partial Immunological and Mitochondrial Recovery after Reducing Didanosine Doses in Patients on Didanosine and Tenofovir-Based Regimens","volume":"13","author":"Negredo","year":"2008","journal-title":"Antivir. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1177\/135965350601100513","article-title":"Short Communication Metabolic and Mitochondrial Effects of Switching Antiretroviral-Experienced Patients to Enfuvirtide, Tenofovir and Saquinavir\/Ritonavir","volume":"11","author":"Garrabou","year":"2006","journal-title":"Antivir. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2174\/157016210791330374","article-title":"Mild Improvement in Mitochondrial Function after a 3-Year Antiretroviral Treatment Interruption despite Persistent Impairment of Mitochondrial DNA Content","volume":"8","author":"Negredo","year":"2010","journal-title":"Curr. HIV Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e126675","DOI":"10.1172\/jci.insight.126675","article-title":"Effect of HIV Infection and Antiretroviral Therapy on Immune Cellular Functions","volume":"4","author":"Korencak","year":"2019","journal-title":"JCI Insight"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/infdis\/jir764","article-title":"The Effects of Sepsis on Mitochondria","volume":"205","author":"Garrabou","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ba\u00f1\u00f3, M., Mor\u00e9n, C., Barroso, S., Ju\u00e1rez, D.L., Guitart-Mampel, M., Gonz\u00e1lez-Casacuberta, I., Canto-Santos, J., Lozano, E., Le\u00f3n, A., and Pedrol, E. (2020). Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-Exposure Prophylaxis in Uninfected Patients. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00497"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1001\/jama.289.22.2978","article-title":"Impact of HIV Infection and HAART on Serum Lipids in Men","volume":"289","author":"Riddler","year":"2003","journal-title":"JAMA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7573\/dic.2021-8-7","article-title":"HIV: How to Manage Dyslipidaemia in HIV","volume":"11","author":"Lee","year":"2022","journal-title":"Drugs Context"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/135965350601100505","article-title":"Mitochondrial (Mt)DNA Changes in Tissue May Not Be Reflected by Depletion of MtDNA in Peripheral Blood Mononuclear Cells in HIV-Infected Patients","volume":"11","author":"Maagaard","year":"2006","journal-title":"Antivir. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.clinbiochem.2008.03.007","article-title":"Analysis of Coenzyme Q10 in Muscle and Fibroblasts for the Diagnosis of CoQ10 Deficiency Syndromes","volume":"41","author":"Montero","year":"2008","journal-title":"Clin. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8418\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:18Z","timestamp":1760110098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":80,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158418"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158418","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,1]]}}}