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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