Lopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis

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dc.contributor.authorMcIlleron H.
dc.contributor.authorRen Y.
dc.contributor.authorNuttall J.
dc.contributor.authorFairlie L.
dc.contributor.authorRabie H.
dc.contributor.authorCotton M.
dc.contributor.authorEley B.
dc.contributor.authorMeyers T.
dc.contributor.authorSmith P.J.
dc.contributor.authorMerry C.
dc.contributor.authorMaartens G.
dc.date.accessioned2011-10-13T16:59:01Z
dc.date.available2011-10-13T16:59:01Z
dc.date.issued2011
dc.description.abstractBackground: Coadministration of rifampicin dramatically reduces the concentrations of protease inhibitors. A pharmacokinetic study in healthy adults showed that doubling the dose of coformulated lopinavir/ritonavir was able to overcome the inducing effect of rifampicin. We evaluated this strategy in children treated with rifampicin-based antituberculosis therapy attending antiretroviral clinics in South Africa. Methods: Plasma concentrations of lopinavir were measured in children (aged 0.64-2.43 years) established on antituberculosis treatment who commenced antiretroviral therapy comprising double the usual recommended dose of lopinavir/ritonavir oral solution (460/115 mg/m2 twice daily) plus two nucleoside reverse transcriptase inhibitors. Control children (0.57-4.23 years old) without tuberculosis received standard doses of lopinavir/ritonavir (230/57.5 mg/m2 twice daily). Results: Pre-dose lopinavir concentrations were reduced by >80% in children with tuberculosis (median 0.7 mg/l, IQR 0.1-2.0) compared with controls (4.2 mg/l, IQR 3.4-8.1; P<0.001) and were below the minimum recommended concentration of 1 mg/l in 12 of 20 (60%) children with tuberculosis versus 2 of 24 (8%) controls (P<0.001). Conclusions: Double doses of coformulated lopinavir/ritonavir results in inadequate lopinavir concentrations in young children treated concurrently with rifampicin. Suitable regimens are urgently needed for treating young children with HIV-associated tuberculosis. ©2011 International Medical Press.
dc.description.versionArticle
dc.identifier.citationAntiviral Therapy
dc.identifier.citation16
dc.identifier.citation3
dc.identifier.citationhttp://www.scopus.com/inward/record.url?eid=2-s2.0-79959450135&partnerID=40&md5=5aa4ad757f56c7f449166e414f438e2b
dc.identifier.issn13596535
dc.identifier.other10.3851/IMP1757
dc.identifier.urihttp://hdl.handle.net/10019.1/16949
dc.subjectlopinavir
dc.subjectlopinavir plus ritonavir
dc.subjectrifampicin
dc.subjectRNA directed DNA polymerase inhibitor
dc.subjectarea under the curve
dc.subjectarticle
dc.subjectchild
dc.subjectclinical article
dc.subjectcontrolled study
dc.subjectdrug blood level
dc.subjectdrug dose increase
dc.subjectdrug exposure
dc.subjectdrug inhibition
dc.subjectdrug monitoring
dc.subjectfemale
dc.subjecthuman
dc.subjectHuman immunodeficiency virus infection
dc.subjectinfant
dc.subjectmale
dc.subjectmaximum plasma concentration
dc.subjectplasma concentration-time curve
dc.subjectpreschool child
dc.subjectpriority journal
dc.subjectrecommended drug dose
dc.subjectSouth Africa
dc.subjecttuberculosis
dc.subjectvirus load
dc.subjectAnti-HIV Agents
dc.subjectAntitubercular Agents
dc.subjectChild, Preschool
dc.subjectDrug Interactions
dc.subjectDrug Therapy, Combination
dc.subjectFemale
dc.subjectHIV
dc.subjectHIV Infections
dc.subjectHumans
dc.subjectInfant
dc.subjectMale
dc.subjectPyrimidinones
dc.subjectRifampin
dc.subjectRitonavir
dc.subjectSouth Africa
dc.subjectTreatment Outcome
dc.subjectTuberculosis
dc.titleLopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis
dc.typeArticle
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