Pharmacokinetics of Once Daily Darunavir/Ritonavir in HIV-infected Children

The EMA and FDA recommended weight band dosing for once daily DRV/r dosing in children 3 -12 years of age has been derived from pharmacokinetic modelling. Results from population pharmacokinetic modelling and simulation in these children predict similar DRV plasma exposures compared to treatment-naïve adults, but has not been formally studied in the target population. Although no clinical trial was conducted to collect exposure-safety data, the predicted exposures from the once daily dosing is supported by exposures observed in a paediatric clinical trial where twice-daily dosing was administered. To validate the weight band based dosing recommendations, we want to evaluate the pharmacokinetics of DRV/r administered once daily, using DRV tablets, in HIV-infected children.

Darunavir/ritonavir is one of the preferred antiretroviral agents as part of combination antiretroviral therapy for treatment of HIV-infected adults according to international guidelines. For children 3-12 years old, FDA has approved once daily dosing of darunavir/ritonavir. Dosing recommendations for children 6-12 years old have been approved based on a modelling and simulation procedure by the company.

This pharmacokinetic study is designed to validate the proposed dosing recommendation for once daily darunavir/ritonavir in HIV-infected children aged 6-12 years old.

Inclusion criteria

• Parents/carers are able and willing to sign the informed consent form prior to screening evaluations
• Subject is HIV infected
• Subject is at least 6 and less than 12 years at day of screening
• Subject has a body weight of at least 15kg
• Subject is able to swallow tablets
• Subject has an undetectable viral load (<50 copies/mL) for the last 6 months prior to screening (at least 2 measurements)
• ART regimen consists of darunavir/ritonavir and 2 NRTIs

Exclusion criteria

• Inability to understand the nature and extent of the trial and the procedures required
• Documented history of sensitivity/idiosyncrasy to darunavir or ritonavir medicinal products or its excipients
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion
• Abnormal renal or liver function (grade 3 or above)
• Participation in a drug trial within 60 days prior to the first dose
• Hemoglobin < 10 g/dL (6.0 mmol/L)
• Children who have previously failed virologically on a PI containing regimen (where virological failure is defined as two successive HIV-1 RNA results >1,000 c/mL more than 24 weeks after starting cART, i.e. changes for toxicity or convenience are not counted as failure)
• Acute illness
• Receiving concomitant therapy except for prophylaxis for opportunistic infections; some treatments may be allowed, but must first be discussed with the principal investigator or project manager.