Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats

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dc.contributor.authorEverson, Fransen_ZA
dc.contributor.authorGenis, Amandaen_ZA
dc.contributor.authorOgundipe, Temitopeen_ZA
dc.contributor.authorDe Boever, Patricken_ZA
dc.contributor.authorGoswami, Nanduen_ZA
dc.contributor.authorLochner, Amandaen_ZA
dc.contributor.authorBlackhurst, Deeen_ZA
dc.contributor.authorStrijdom, Hansen_ZA
dc.date.accessioned2018-12-10T06:18:47Z
dc.date.available2018-12-10T06:18:47Z
dc.date.issued2018-12-05
dc.descriptionCITATION: Everson, F. et al. 2018. Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats. PLoS One, 13(12):e0208537, doi:10.1371/journal.pone.0208537.
dc.descriptionThe original publication is available at https://journals.plos.org/plosone
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund.
dc.description.abstractHIV-infection, certain antiretroviral drug classes, especially protease inhibitors (PI), and obesity are associated with increased ischaemic heart disease (IHD) risk. However, the effect of PI-free fixed dose combination (FDC) antiretroviral therapy (ART) on hearts exposed to ischaemia-reperfusion injury (I/R) is unknown, particularly in obesity. This is becoming relevant as World Health Organisation guidelines recommend a FDC ART containing (non-) nucleoside reverse transcriptase inhibitors (tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) as first-line HIV treatment. Additionally, obesity rates are rising in HIV-infected populations, not only in ART-experienced individuals, but also at the time of ART initiation, which may further increase the risk of IHD. Therefore, we investigated the effects of PI-free FDC ART in myocardial I/R-exposed hearts from obese rats. Obesity was induced in male wistar rats via a 16-week high calorie diet. At week 10, treatment with a FDC ART drug containing TDF/FTC/EFV was initiated. Biometric and metabolic parameters, as well as myocardial functional recovery and infract size (IS), and myocardial signalling proteins following I/R were assessed after 16 weeks. Obese rats presented with increased body and intraperitoneal fat mass, elevated triglyceride and TBARS levels, whilst the hearts responded to I/R with impaired functional performance and increased IS. The FDC ART treatment did not alter biometric and metabolic parameters in obese rats. In a novel finding, ART protected obese hearts against I/R as shown by improved functional performance and smaller IS vs. untreated obese hearts. Cardioprotection was underscored by increased myocardial phosphorylated endothelial nitric oxide synthase (eNOS) and reduced AMP-kinase levels. In conclusion, these results demonstrate for the first time, that 6-weeks treatment of obese rats with a FDC ART drug specifically containing TDF/FTC/EFV conferred cardioprotection against I/R. The FDC ART-induced cardioprotection was seemingly unrelated to metabolic changes, but rather due to direct cardiac mechanisms including the up-regulation of myocardial eNOS.en_ZA
dc.description.sponsorshipSouth African National Research Foundation
dc.description.sponsorshipHarry Crossley Foundation
dc.description.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208537
dc.description.versionPublisher's version
dc.format.extent27 pages
dc.identifier.citationEverson, F. et al. 2018. Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats. PLoS One, 13(12):e0208537, doi:10.1371/journal.pone.0208537.
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0208537
dc.identifier.urihttp://hdl.handle.net/10019.1/105127
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectTenofoviren_ZA
dc.subjectAntiretroviral therapyen_ZA
dc.subjectEmtricitabineen_ZA
dc.subjectEfavirenzen_ZA
dc.subjectHIV Infectionsen_ZA
dc.subjectCoronary heart diseaseen_ZA
dc.subjectObesityen_ZA
dc.titleTreatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese ratsen_ZA
dc.typeArticleen_ZA
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