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Lopinavir Exposure is Insufficient in Children Given Double Doses of Lopinavir/Ritonavir during Rifampicin-Based Treatment for Tuberculosis

2010; SAGE Publishing; Volume: 16; Issue: 3 Linguagem: Inglês

10.3851/imp1757

2040-2058

Helen McIlleron, Yuan Ren, James Nuttall, Lee Fairlie, Helena Rabie, Mark F. Cotton, Brian Eley, Tammy Meyers, Peter J. Smith, Concepta Merry, Gary Maartens,

Tuberculosis Research and Epidemiology

Background 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/ m 2 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/m 2 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.