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

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

Corresponding author name: Helen McIlleron
Corresponding author e-mail: helen.mcilleron@uct.ac.za

Citation: Antiviral Therapy 2011; 16:417-421
doi: 10.3851/IMP1757

Date accepted: 09 September 2010
Date published online: 18 March 2011

Abstract

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/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.

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