Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients

Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading...

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Autores: Bañó, Maria, Morén Núñez, Constanza, Barroso, Sergio, Juárez Flores, Diana Luz, Guitart Mampel, Mariona, González Casacuberta, Ingrid, Cantó Santos, Judith, Lozano Garcia, Ester, León, Agathe, Pedrol, Enric, Miró i Andreu, Òscar, Tobías, Ester, Mallolas Masferrer, Josep, Rojas, Jhon F., Cardellach, Francesc, Martínez, Esteban, Garrabou Tornos, Glòria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173622
Acceso en línea:https://hdl.handle.net/2445/173622
Access Level:acceso abierto
Palabra clave:VIH (Virus)
Antiretrovirals
HIV (Viruses)
Antiretroviral agents
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spelling Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected PatientsBañó, MariaMorén Núñez, ConstanzaBarroso, SergioJuárez Flores, Diana LuzGuitart Mampel, MarionaGonzález Casacuberta, IngridCantó Santos, JudithLozano Garcia, EsterLeón, AgathePedrol, EnricMiró i Andreu, ÒscarTobías, EsterMallolas Masferrer, JosepRojas, Jhon F.Cardellach, FrancescMartínez, EstebanGarrabou Tornos, GlòriaVIH (Virus)AntiretroviralsHIV (Viruses)Antiretroviral agentsBackground: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (−17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.Frontiers Media2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/173622Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fgene.2020.00497Frontiers In Genetics, 2020, vol. 11, p. 497-507https://doi.org/10.3389/fgene.2020.00497cc-by (c) Bañó, Maria et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1736222026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
title Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
spellingShingle Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
Bañó, Maria
VIH (Virus)
Antiretrovirals
HIV (Viruses)
Antiretroviral agents
title_short Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
title_full Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
title_fullStr Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
title_full_unstemmed Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
title_sort Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients
dc.creator.none.fl_str_mv Bañó, Maria
Morén Núñez, Constanza
Barroso, Sergio
Juárez Flores, Diana Luz
Guitart Mampel, Mariona
González Casacuberta, Ingrid
Cantó Santos, Judith
Lozano Garcia, Ester
León, Agathe
Pedrol, Enric
Miró i Andreu, Òscar
Tobías, Ester
Mallolas Masferrer, Josep
Rojas, Jhon F.
Cardellach, Francesc
Martínez, Esteban
Garrabou Tornos, Glòria
author Bañó, Maria
author_facet Bañó, Maria
Morén Núñez, Constanza
Barroso, Sergio
Juárez Flores, Diana Luz
Guitart Mampel, Mariona
González Casacuberta, Ingrid
Cantó Santos, Judith
Lozano Garcia, Ester
León, Agathe
Pedrol, Enric
Miró i Andreu, Òscar
Tobías, Ester
Mallolas Masferrer, Josep
Rojas, Jhon F.
Cardellach, Francesc
Martínez, Esteban
Garrabou Tornos, Glòria
author_role author
author2 Morén Núñez, Constanza
Barroso, Sergio
Juárez Flores, Diana Luz
Guitart Mampel, Mariona
González Casacuberta, Ingrid
Cantó Santos, Judith
Lozano Garcia, Ester
León, Agathe
Pedrol, Enric
Miró i Andreu, Òscar
Tobías, Ester
Mallolas Masferrer, Josep
Rojas, Jhon F.
Cardellach, Francesc
Martínez, Esteban
Garrabou Tornos, Glòria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv VIH (Virus)
Antiretrovirals
HIV (Viruses)
Antiretroviral agents
topic VIH (Virus)
Antiretrovirals
HIV (Viruses)
Antiretroviral agents
description Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (−17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.
publishDate 2020
dc.date.none.fl_str_mv 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 https://hdl.handle.net/2445/173622
url https://hdl.handle.net/2445/173622
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fgene.2020.00497
Frontiers In Genetics, 2020, vol. 11, p. 497-507
https://doi.org/10.3389/fgene.2020.00497
dc.rights.none.fl_str_mv cc-by (c) Bañó, Maria et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Bañó, Maria et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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