The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy

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dc.contributor.authorDecloedt, Eric Hen_ZA
dc.contributor.authorMaartens, Garyen_ZA
dc.contributor.authorSmith, Peteren_ZA
dc.contributor.authorMerry, Conceptaen_ZA
dc.contributor.authorBango, Funekaen_ZA
dc.contributor.authorMcIlleron, Helenen_ZA
dc.date.accessioned2015-11-23T12:36:18Z
dc.date.available2015-11-23T12:36:18Z
dc.date.issued2012en_ZA
dc.description.abstractObjective Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment. METHODS: Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month. RESULTS: 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1-9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable. CONCLUSION: Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate.en_ZA
dc.identifier.apacitationDecloedt, E. H., Maartens, G., Smith, P., Merry, C., Bango, F., & McIlleron, H. (2012). The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. <i>PLoS One</i>, http://hdl.handle.net/11427/15332en_ZA
dc.identifier.chicagocitationDecloedt, Eric H, Gary Maartens, Peter Smith, Concepta Merry, Funeka Bango, and Helen McIlleron "The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/15332en_ZA
dc.identifier.citationDecloedt, E. H., Maartens, G., Smith, P., Merry, C., Bango, F., & McIlleron, H. (2012). The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. PloS one, 7(3), e32173. doi:10.1371/journal.pone.0032173en_ZA
dc.identifier.ris TY - Journal Article AU - Decloedt, Eric H AU - Maartens, Gary AU - Smith, Peter AU - Merry, Concepta AU - Bango, Funeka AU - McIlleron, Helen AB - Objective Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment. METHODS: Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month. RESULTS: 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1-9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable. CONCLUSION: Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0032173 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy TI - The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy UR - http://hdl.handle.net/11427/15332 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15332
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0032173
dc.identifier.vancouvercitationDecloedt EH, Maartens G, Smith P, Merry C, Bango F, McIlleron H. The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. PLoS One. 2012; http://hdl.handle.net/11427/15332.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2012 Decloedt et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherAntiretroviral therapyen_ZA
dc.subject.otherViral loaden_ZA
dc.subject.otherAdverse eventsen_ZA
dc.subject.otherToxicityen_ZA
dc.subject.otherAdultsen_ZA
dc.subject.otherDrug metabolismen_ZA
dc.subject.otherDrug therapyen_ZA
dc.titleThe safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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