{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:25:34Z","timestamp":1789770334393,"version":"4.0.1"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007671","name":"Fundaci\u00f3n para la Investigaci\u00f3n y la Prevenci\u00f3n del Sida en Espa\u00f1a","doi-asserted-by":"publisher","award":["FIPSE 360982\/10"],"award-info":[{"award-number":["FIPSE 360982\/10"]}],"id":[{"id":"10.13039\/501100007671","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria","award":["FIS 01738\/13, FIS 01455\/13, PI00005\/14, PI00817\/15, PI00903\/15 and PI00130\/15"],"award-info":[{"award-number":["FIS 01738\/13, FIS 01455\/13, PI00005\/14, PI00817\/15, PI00903\/15 and PI00130\/15"]}]},{"name":"CIBERER and InterCIBER","award":["PIE1400061"],"award-info":[{"award-number":["PIE1400061"]}]},{"name":"Suports a Grups de Recerca","award":["SGR 2014\/376 and 2014\/SGR928"],"award-info":[{"award-number":["SGR 2014\/376 and 2014\/SGR928"]}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["87\/C\/2015"],"award-info":[{"award-number":["87\/C\/2015"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0216712","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T18:37:16Z","timestamp":1558636636000},"page":"e0216712","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7504-4794","authenticated-orcid":true,"given":"Sergio","family":"Barroso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanza","family":"Mor\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c0lex","family":"Gonz\u00e1lez-Segura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Riba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan A.","family":"Arnaiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Manriquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemina","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Larousse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Lonc\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa de","family":"Lazzari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Llopis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Mallolas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Mir\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Carn\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Gatell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gl\u00f2ria","family":"Garrabou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"ref1","first-page":"827","article-title":"CLINICIAN \u2018 S CORNER Treatment for Adult HIV Infection","volume":"296","author":"SM Hammer","year":"2006","journal-title":"J Am Med Assoc"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinf.2008.05.006","article-title":"New treatment options for HIV salvage patients: An overview of second generation PIs, NNRTIs, integrase inhibitors and CCR5 antagonists","author":"A Hughes","year":"2008","journal-title":"Journal of Infection"},{"key":"ref3","article-title":"The use of antiretroviral drugs for treating and preventing HIV infection","author":"CG WHO","year":"2016","journal-title":"World Heal Organ"},{"key":"ref4","first-page":"1","article-title":"Nephropharmacology for the Clinician Clinical Pharmacology in HIV Therapy","author":"MG Atta","year":"2018","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/S0140-6736(99)06102-4","article-title":"Mitochondrial toxicity induced by nucleoside-analogue reverse- transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy","volume":"354","author":"K Brinkman","year":"1999","journal-title":"Lancet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1097\/00002030-200203290-00002","article-title":"Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study","volume":"16","author":"Noor M a","year":"2002","journal-title":"AIDS"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1177\/135965350400900609","article-title":"Complications associated with NRTI therapy: update on clinical features and possible pathogenic mechanisms","volume":"9","author":"D Nolan","year":"2004","journal-title":"Antivir Ther"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1086\/429697","article-title":"In vivo, nucleoside reverse-transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA","volume":"191","author":"PWG Mallon","year":"2005","journal-title":"J Infect Dis"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1097\/01.aids.0000244200.11006.55","article-title":"Effects of atazanavir\/ritonavir and lopinavir\/ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically","volume":"20","author":"Flint OP Noor M a","year":"2006","journal-title":"AIDS"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa062744","article-title":"Class of antiretroviral drugs and the risk of myocardial infarction","volume":"356","author":"N Friis-M\u00f8ller","year":"2007","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/QAI.0b013e31829bdb67","article-title":"Differentially altered molecular signature of visceral adipose tissue in HIV-1-associated lipodystrophy","volume":"64","author":"JM Gallego-Escuredo","year":"2013","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s40264-016-0417-x","article-title":"Drug-Induced Mitochondrial Toxicity","volume":"39","author":"IP Hargreaves","year":"2016","journal-title":"Drug Saf"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/S0140-6736(98)03391-1","article-title":"Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance","volume":"351","author":"A Carr","year":"1998","journal-title":"Lancet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"S135","DOI":"10.1086\/313854","article-title":"HIV Protease Inhibitor-Related Lipodystrophy Syndrome","volume":"30","author":"A. Carr","year":"2000","journal-title":"Clin Infect Dis"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0140-6736(00)04056-3","article-title":"Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study","volume":"357","author":"E Martinez","year":"2001","journal-title":"Lancet"},{"key":"ref16","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":"AM Margolis","year":"2014","journal-title":"J Med Toxicol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1089\/aid.2005.21.702","article-title":"Short communication: HIV infection, antiretrovirals, and apoptosis: studies on skeletal muscle","volume":"21","author":"O Miro","year":"2005","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1086\/605440","article-title":"Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA)","volume":"49","author":"E Negredo","year":"2009","journal-title":"Clin Infect Dis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/QAI.0b013e318250455e","article-title":"Mitochondrial evolution in HIV-infected children receiving first- or second-generation nucleoside analogues","volume":"60","author":"C Mor\u00e9n","year":"2012","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref20","first-page":"515","article-title":"Reverse transcriptase inhibitors alter uncoupling protein-1 and mitochondrial biogenesis in brown adipocytes","volume":"10","author":"ML Rodr\u00edguez","year":"2005"},{"key":"ref21","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":"KK Ganta","year":"2017","journal-title":"Cell Biol Toxicol. Cell Biology and Toxicology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1128\/AAC.46.8.2687-2691.2002","article-title":"Induction of apoptosis by a nonnucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitor","volume":"46","author":"Lum JJ Pilon a a","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10156-010-0101-5","article-title":"Comparison of the influence of four classes of HIV antiretrovirals on adipogenic differentiation: The minimal effect of raltegravir and atazanavir","volume":"17","author":"R Minami","year":"2011","journal-title":"J Infect Chemother"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1128\/AAC.00104-12","article-title":"Effects of rilpivirine on human adipocyte differentiation, gene expression, and release of adipokines and cytokines","volume":"56","author":"J D\u00edaz-Delf\u00edn","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1468-1293.2008.00552.x","article-title":"Hepatotoxicity of nevirapine in virologically suppressed patients according to gender and CD4 cell counts","volume":"9","author":"E De Lazzari","year":"2008","journal-title":"HIV Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1056\/NEJMoa035211","article-title":"Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia","volume":"348","author":"A Lazzarin","year":"2003","journal-title":"N Engl J Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/j.1745-7254.2005.00193.x","article-title":"HIV entry inhibitors: A new generation of antiretroviral drugs","volume":"26","author":"E Krambovitis","year":"2005","journal-title":"Acta Pharmacol Sin"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2165\/00003495-200565080-00007","article-title":"Enfuvirtide: A review of its use in the management of HIV infection","author":"V Oldfield","year":"2005","journal-title":"Drugs"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1517\/13543784.15.12.1507","article-title":"A historical sketch of the discovery and development of HIV-1 integrase inhibitors","volume":"15","author":"A. Savarino","year":"2006","journal-title":"Expert Opin Investig Drugs"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1093\/cid\/civ366","article-title":"Raltegravir in HIV-llnfected Pregnant Women: Pharmacokinetics, Safety and Efficacy","volume":"61","author":"MI Blonk","year":"2015","journal-title":"Clin Infect Dis"},{"key":"ref31","article-title":"Placental Mitochondrial Toxicity, Oxidative Stress, Apoptosis, and Adverse Perinatal Outcomes in HIV Pregnancies Under Antiretroviral Treatment Containing Zidovudine","volume":"75","author":"S Hern\u00e1ndez","year":"2017","journal-title":"JAIDS J Acquir Immune Defic Syndr"},{"key":"ref32","first-page":"41","article-title":"Are new antiretroviral treatments increasing the risks of clinical obesity?","author":"A Hill","year":"2019"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"e0209911","DOI":"10.1371\/journal.pone.0209911","article-title":"Body composition and adipokines changes after initial treatment with darunavir-ritonavir plus either raltegravir or tenofovir disoproxil fumarate-emtricitabine: A substudy of the NEAT001\/ANRS143 randomised trial","volume":"14","author":"Bernardino","year":"2019","journal-title":"PLoS One. Public Library of Science"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/M14-1084","article-title":"Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial","volume":"161","author":"JL Lennox","year":"2014","journal-title":"Ann Intern Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1056\/NEJMra041811","article-title":"Cardiovascular risk and body-fat abnormalities in HIV-infected adults","volume":"352","author":"S Grinspoon","year":"2005","journal-title":"N Engl J Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1002\/sim.1207","article-title":"Meta-analysis combining parallel and cross-over clinical trials. III: The issue of carry-over","volume":"21","author":"F Curtin","year":"2002","journal-title":"Stat Med"},{"key":"ref37","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":"G Garrabou","year":"2009","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/clinchem\/40.4.574","article-title":"Biological variability of cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B","volume":"40","author":"SM Marcovina","year":"1994","journal-title":"Clin Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"845","DOI":"10.2165\/00002018-200730100-00004","article-title":"Mitochondrial disorders among infants exposed to HIV and antiretroviral therapy","volume":"30","author":"MJ Funk","year":"2007","journal-title":"Drug Saf"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1177\/0192623313503519","article-title":"HIV Treatment and Associated Mitochondrial Pathology: Review of 25 Years of in Vitro, Animal, and Human Studies","volume":"42","author":"K Gardner","year":"2013","journal-title":"Toxicol Pathol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1038\/aps.2017.54","article-title":"Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp","volume":"38","author":"F Wang","year":"2017","journal-title":"Acta Pharmacol Sin"},{"issue":"6","key":"ref42","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.3390\/v6083181","article-title":"Human Immunodeficiency Virus-1 (HIV-1)-Mediated apoptosis: new therapeutic targets","volume":"19","author":"Z Mbita","year":"2014","journal-title":"Viruses"},{"key":"ref43","first-page":"1","article-title":"Incidence and risk factors for liver enzymes elevations in highly treatment-experienced patients switching from enfuvirtide to raltegravir: a sub-study of the ANRS-138 EASIER trial","volume":"2","author":"N De Castro","year":"2016","journal-title":"AIDS Res Ther. BioMed Central"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/14740338.2018.1411903","article-title":"A safety evaluation of raltegravir for the treatment of HIV","volume":"17","author":"R de Miguel","year":"2018","journal-title":"Expert Opin Drug Saf"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s11096-016-0316-3","article-title":"Continuous intravenous infusion of enfuvirtide in a patient with a multidrug-resistant HIV strain","volume":"38","author":"RW Neijzen","year":"2016","journal-title":"Int J Clin Pharm"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3851\/IMP1652","article-title":"Clinical perspective on antiretroviral drug-drug interactions with the non-nucleoside reverse transcriptase inhibitor etravirine","author":"TN Kakuda","year":"2010","journal-title":"Antiviral Therapy"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jcv.2003.10.006","article-title":"Safety, tolerability, and plasma pharmacokinetics of high-strength formulations of enfuvirtide (T-20) in treatment-experienced HIV-1-infected patients","volume":"30","author":"DA Wheeler","year":"2004","journal-title":"J Clin Virol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0140-6736(07)60597-2","article-title":"Articles Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial","volume":"369","author":"B Grinsztejn","year":"2007","journal-title":"Lancet"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/jac\/dkp446","article-title":"Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C","author":"E Vispo","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"ref50","article-title":"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","volume":"9","author":"M Gallego-escuredo","year":"2014","journal-title":"PLoS One"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/jac\/dkr269","article-title":"Efficacy and safety of raltegravir in treatment-experienced HIV-1-infected patients switching from enfuvirtide-based regimens: 48 week results of the randomized easier ANRS 138 trial","volume":"66","author":"\u015a Gallien","year":"2011","journal-title":"J Antimicrob Chemother"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/QAI.0b013e31824bb720","article-title":"Long-term efficacy and safety of raltegravir, etravirine, and darunavir\/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial","volume":"59","author":"C Fagard","year":"2012","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMsr077003","article-title":"Statistics in Medicine\u2014Reporting of Subgroup Analyses in Clinical Trials","volume":"357","author":"R Wang","year":"2007","journal-title":"N Engl J Med"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7742(08)00001-9","article-title":"Gender Differences in Pharmacological Response","volume":"83","author":"GD Anderson","year":"2008","journal-title":"Int Rev Neurobiol"},{"key":"ref55","article-title":"Estrogens regulate life and death in mitochondria","author":"CM Klinge","year":"2017","journal-title":"Journal of Bioenergetics and Biomembranes"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0216712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T14:38:15Z","timestamp":1663511895000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0216712"}},"subtitle":[],"editor":[{"given":"Alan","family":"Winston","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,5,23]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0216712","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,23]]}}}