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.
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.
Authors: Shirin Heidari; Lynne M Mofenson; Charlotte V Hobbs; Mark F Cotton; Richard Marlink; Elly Katabira Journal: J Acquir Immune Defic Syndr Date: 2012-02-01 Impact factor: 3.731
Authors: Chao Zhang; Paolo Denti; Eric H Decloedt; Yuan Ren; Mats O Karlsson; Helen McIlleron Journal: Br J Clin Pharmacol Date: 2013-11 Impact factor: 4.335
Authors: Chao Zhang; Helen McIlleron; Yuan Ren; Jan-Stefan van der Walt; Mats O Karlsson; Ulrika S H Simonsson; Paolo Denti Journal: Antivir Ther Date: 2012
Authors: Chao Zhang; Paolo Denti; Eric Decloedt; Gary Maartens; Mats O Karlsson; Ulrika S H Simonsson; Helen McIlleron Journal: Br J Clin Pharmacol Date: 2012-05 Impact factor: 4.335
Authors: Mutsa Bwakura Dangarembizi; Pearl Samson; Edmund V Capparelli; Carolyn Bolton Moore; Patrick Jean-Philippe; Stephen A Spector; Nahida Chakhtoura; Alex Benns; Bonnie Zimmer; Lynette Purdue; Chivon Jackson; Carole Wallis; Jennifer L Libous; Ellen G Chadwick Journal: J Acquir Immune Defic Syndr Date: 2019-08-01 Impact factor: 3.731