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

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/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: Helen McIlleron, Yuan Ren, James Nuttall, Lee Fairlie, Helena Rabie, Mark Cotton, Brian Eley, Tammy Meyers, Peter J Smith, Concepta Merry, Gary Maartens
• Journal: Antiviral therapy (Antivir Ther) Vol. 16 Issue 3 Pg. 417-21 ( 2011) ISSN: 2040-2058 [Electronic] England
• PMID: 21555825 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Antitubercular Agents
• Pyrimidinones
• Lopinavir
• Ritonavir
• Rifampin

Topics

• Anti-HIV Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Antitubercular Agents (administration & dosage, therapeutic use)
• Child, Preschool
• Drug Interactions
• Drug Therapy, Combination
• Female
• HIV
• HIV Infections (complications, drug therapy, virology)
• Humans
• Infant
• Lopinavir
• Male
• Pyrimidinones (administration & dosage, pharmacokinetics, therapeutic use)
• Rifampin (administration & dosage, therapeutic use)
• Ritonavir (administration & dosage, pharmacokinetics, therapeutic use)
• South Africa
• Treatment Outcome
• Tuberculosis (drug therapy)