Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers

Context: Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antir...

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Autores: Barroso, Sergio, Morén, Constanza, González Segura, Àlex, Riba, Neus, Arnaiz, Joan A., Manriquez, Marcela, Santana, Gemina, Blanco, José L., Larousse, María, Loncà, Montserrat, Lazzari, Elisa de, Llopis, Jaume, Mallolas, Josep, Miró, Òscar, Carné, Xavier, Gatell, Josep M., Garrabou, Glòria, Martínez, Esteban
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/45124
Acesso em linha:http://hdl.handle.net/10230/45124
http://dx.doi.org/10.1371/journal.pone.0216712
Access Level:acceso abierto
Palavra-chave:Toxicity
Mitochondria
Antiretrovirals
Drug metabolism
Mitochondrial DNA
Antiretroviral therapy
Cholesterol
Insulin resistance
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spelling Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteersBarroso, SergioMorén, ConstanzaGonzález Segura, ÀlexRiba, NeusArnaiz, Joan A.Manriquez, MarcelaSantana, GeminaBlanco, José L.Larousse, MaríaLoncà, MontserratLazzari, Elisa deLlopis, JaumeMallolas, JosepMiró, ÒscarCarné, XavierGatell, Josep M.Garrabou, GlòriaMartínez, EstebanToxicityMitochondriaAntiretroviralsDrug metabolismMitochondrial DNAAntiretroviral therapyCholesterolInsulin resistanceContext: Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antiretrovirals, we assessed markers of these toxicities in healthy adult volunteers treated with Enfuvirtide (T20) or Raltegravir (RAL). Methods: Twenty-six healthy participants were randomized to T20/90mg vs. placebo (n = 12) or RAL/400mg vs. placebo (n = 14) every 12h in two 7-day periods separated by a 4-week washout period. Major end-points were changes in lipid profile (total cholesterol, high-density-lipoprotein (HDL)-cholesterol, low-density-lipoprotein (LDL)-cholesterol, triglycerides), insulin resistance (glucose) and mitochondrial toxicity (mitochondrial DNA content-mtDNA-in peripheral blood mononuclear cells). Renal and hepatic toxicity (creatinine, alanine transaminase (AST), alanine aminotransferase (ALT), bilirubin and total plasma proteins) and overall safety were also analysed. Effect of period, treatment, and basal measures were evaluated for each end-point. Results: Neither T20-administration nor RAL-administration yielded to any statistic significant change in the markers of metabolic, mitochondrial, renal or hepatic toxicity assessed. No symptoms indicative of drug toxicity were neither found in any subject. Conclusions: In absence of HIV infection, or concomitant treatment, short-term exposure to T20 or RAL in healthy adult volunteers did not lead to any indicative changes in toxicity markers thus presuming the safe profile of both drugs.Public Library of Science (PLoS)202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45124http://dx.doi.org/10.1371/journal.pone.0216712reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPLoS One. 2019; 14(5):e0216712© 2019 Barroso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/451242026-05-29T05:05:01Z
dc.title.none.fl_str_mv Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
title Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
spellingShingle Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
Barroso, Sergio
Toxicity
Mitochondria
Antiretrovirals
Drug metabolism
Mitochondrial DNA
Antiretroviral therapy
Cholesterol
Insulin resistance
title_short Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
title_full Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
title_fullStr Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
title_full_unstemmed Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
title_sort Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers
dc.creator.none.fl_str_mv Barroso, Sergio
Morén, Constanza
González Segura, Àlex
Riba, Neus
Arnaiz, Joan A.
Manriquez, Marcela
Santana, Gemina
Blanco, José L.
Larousse, María
Loncà, Montserrat
Lazzari, Elisa de
Llopis, Jaume
Mallolas, Josep
Miró, Òscar
Carné, Xavier
Gatell, Josep M.
Garrabou, Glòria
Martínez, Esteban
author Barroso, Sergio
author_facet Barroso, Sergio
Morén, Constanza
González Segura, Àlex
Riba, Neus
Arnaiz, Joan A.
Manriquez, Marcela
Santana, Gemina
Blanco, José L.
Larousse, María
Loncà, Montserrat
Lazzari, Elisa de
Llopis, Jaume
Mallolas, Josep
Miró, Òscar
Carné, Xavier
Gatell, Josep M.
Garrabou, Glòria
Martínez, Esteban
author_role author
author2 Morén, Constanza
González Segura, Àlex
Riba, Neus
Arnaiz, Joan A.
Manriquez, Marcela
Santana, Gemina
Blanco, José L.
Larousse, María
Loncà, Montserrat
Lazzari, Elisa de
Llopis, Jaume
Mallolas, Josep
Miró, Òscar
Carné, Xavier
Gatell, Josep M.
Garrabou, Glòria
Martínez, Esteban
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Toxicity
Mitochondria
Antiretrovirals
Drug metabolism
Mitochondrial DNA
Antiretroviral therapy
Cholesterol
Insulin resistance
topic Toxicity
Mitochondria
Antiretrovirals
Drug metabolism
Mitochondrial DNA
Antiretroviral therapy
Cholesterol
Insulin resistance
description Context: Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antiretrovirals, we assessed markers of these toxicities in healthy adult volunteers treated with Enfuvirtide (T20) or Raltegravir (RAL). Methods: Twenty-six healthy participants were randomized to T20/90mg vs. placebo (n = 12) or RAL/400mg vs. placebo (n = 14) every 12h in two 7-day periods separated by a 4-week washout period. Major end-points were changes in lipid profile (total cholesterol, high-density-lipoprotein (HDL)-cholesterol, low-density-lipoprotein (LDL)-cholesterol, triglycerides), insulin resistance (glucose) and mitochondrial toxicity (mitochondrial DNA content-mtDNA-in peripheral blood mononuclear cells). Renal and hepatic toxicity (creatinine, alanine transaminase (AST), alanine aminotransferase (ALT), bilirubin and total plasma proteins) and overall safety were also analysed. Effect of period, treatment, and basal measures were evaluated for each end-point. Results: Neither T20-administration nor RAL-administration yielded to any statistic significant change in the markers of metabolic, mitochondrial, renal or hepatic toxicity assessed. No symptoms indicative of drug toxicity were neither found in any subject. Conclusions: In absence of HIV infection, or concomitant treatment, short-term exposure to T20 or RAL in healthy adult volunteers did not lead to any indicative changes in toxicity markers thus presuming the safe profile of both drugs.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/45124
http://dx.doi.org/10.1371/journal.pone.0216712
url http://hdl.handle.net/10230/45124
http://dx.doi.org/10.1371/journal.pone.0216712
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS One. 2019; 14(5):e0216712
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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