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dc.contributor.authorAnnamalai, Lakshmanan
dc.contributor.authorWestmoreland, Susan V.
dc.contributor.authorDomingues, Heber
dc.contributor.authorWalsh, Dennis G.
dc.contributor.authorGonzalez, Ramon Gilberto
dc.contributor.authorO'Neil, Shawn P.
dc.date.accessioned2011-04-23T01:28:35Z
dc.date.issued2010
dc.identifier.citationAnnamalai, Lakshmanan, Susan V. Westmoreland, Heber G. Domingues, Dennis G. Walsh, R. Gilberto Gonzalez, and Shawn P. O'Neil. 2010. Myocarditis in CD8-depleted SIV-infected Rhesus Macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors. PLoS ONE 5(12): e14429.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4874774
dc.description.abstractBackground: Although highly active antiretroviral therapy (HAART) has dramatically reduced the morbidity and mortality associated with HIV infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (NRTIs). Current treatment guidelines recommend the use of HAART regimens containing two NRTIs for initial therapy of HIV-1 positive individuals; however, potential cardiotoxicity resulting from treatment with multiple NRTIs has not been addressed. Methodology/Principal Findings: We examined myocardial tissue from twelve CD8 lymphocyte-depleted adult rhesus macaques, including eight animals infected with simian immunodeficiency virus, four of which received combined antiretroviral therapy (CART) consisting of two NRTIs [(9-R-2-Phosphonomethoxypropyl Adenine) (PMPA) and (+/−)-beta-2′,3′-dideoxy-5-fluoro-3′-thiacytidine (RCV)] for 28 days. Multifocal infiltrates of mononuclear inflammatory cells were present in the myocardium of all macaques that received CART, but not untreated SIV-positive animals or SIV-negative controls. Macrophages were the predominant inflammatory cells within lesions, as shown by immunoreactivity for the macrophage markers Iba1 and CD68. Heart specimens from monkeys that received CART had significantly lower virus burdens than untreated animals (p<0.05), but significantly greater quantities of TNF-α mRNA than either SIV-positive untreated animals or uninfected controls (p<0.05). Interferon-γ (IFN-γ), IL-1β and CXCL11 mRNA were upregulated in heart tissue from SIV-positive monkeys, independent of antiretroviral treatment, but CXCL9 mRNA was only upregulated in heart tissue from macaques that received CART. Conclusions/Significance: These results suggest that short-term treatment with multiple NRTIs may be associated with myocarditis, and demonstrate that the CD8-depleted SIV-positive rhesus monkey is a useful model for studying the cardiotoxic effects of combined antiretroviral therapy in the setting of immunodeficiency virus infection.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0014429en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009713/pdf/en_US
dash.licenseLAA
dc.subjectvirologyen_US
dc.subjectanimal models of infectionen_US
dc.subjecthost antiviral responsesen_US
dc.subjectimmunodeficiency virusesen_US
dc.subjectnew therapies, including antivirals and immunotherapyen_US
dc.subjectcardiovascular disordersen_US
dc.subjectheart failureen_US
dc.subjectinfectious diseasesen_US
dc.subjectHIV infection and AIDSen_US
dc.titleMyocarditis in CD8-Depleted SIV-Infected Rhesus Macaques after Short-Term Dual Therapy with Nucleoside and Nucleotide Reverse Transcriptase Inhibitorsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorWestmoreland, Susan V.
dc.date.available2011-04-23T01:28:35Z
dash.affiliation.otherHMS^Pathologyen_US
dc.identifier.doi10.1371/journal.pone.0014429*
dash.contributor.affiliatedDomingues, Heber
dash.contributor.affiliatedWestmoreland, Susan V.
dash.contributor.affiliatedGonzalez, Ramon


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