koncert a kaletra once daily randomised trial of the pharmacokinetics, safety and efficacy of twice-daily versus once-daily lopinavir/ritonavir tablets dosed by weight as part of combination antiretroviral therapy in human immunodeficiency virus-1 (hiv-1) infected children (penta 18)

Conditions: Antiretroviral Therapy in HIV-1 Infected Children

Summary: the trial will evaluate the pharmacokinetics, safety, efficacy and acceptability of twice- and once-daily dosing of lopinavir/ritonavir tablets (kaletra) dosed by weight in hiv-1 infected children who are currently taking lopinavir/ritonavir as part of their combination antiretroviral therapy and who are currently achieving virological suppression (\<50 copies/ml). specifically: * to confirm weight-based dosing recommendations by evaluating the pharmacokinetics of twice-daily lopinavir/ritonavir half strength formulation tablets dosed on body weight and comparing to historical adult and paediatric data of pharmacokinetics of lopinavir/ritonavir soft gel capsules and oral solution respectively (1, 2). * to compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children. * to evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression at 48 weeks. adherence and acceptability will also be compared.


Eligibility criteria:
inclusion criteria: * aged \<18 years (up to 18th birthday) with confirmed hiv-1 infection * weight ≥15 kg * able to swallow tablets * stable (i.e. cd4 not declining) on a combination antiretroviral regimen that has included lopinavir/ritonavir for at least 24 weeks * taking lopinavir/ritonavir dosed twice-daily and be willing at the screening visit to change to tablet formulation (if not currently taking tablets) and to change the lopinavir/ritonavir dose to follow the recommended fda dosing plan based on body weight bands as necessary (see 7.2.2); if participating in the pk study\*, be willing at the screening visit to change to lopinavir/ritonavir half strength formulation tablets (100/25mg) only, dosed twice-daily and change the lopinavir/ritonavir dose to follow the recommended fda dosing plan based on body weight bands as necessary (see 7.2.1) * viral suppression (hiv-1 rna \<50 copies/ml) for at least the prior 24 weeks (minimum of 2 measurements). * children and caregivers willing to participate in the pk study if they are among a minimum of the first 16 children enrolled in each body weight band in the trial, including a second pk assessment if randomised to switch to once-daily lopinavir/ritonavir. * parents/carers and children, where applicable, give informed written consent exclusion criteria: * children on an antiretroviral regimen that includes a non-nucleoside reverse transcriptase inhibitor (nnrti), fosamprenavir or nelfinavir * children who have previously failed virologically on a protease inhibitor (pi) containing regimen (where virological failure is defined as two successive hiv-1 rna results\>1000 copies/ml (confirmed) more than 24 weeks after starting highly active antiretroviral therapy (haart), i.e changes for toxicity are not counted as failure) * acute illness * abnormal renal or liver function (grade 3 or above) * receiving concomitant therapy except for prophylaxis; some treatments may be allowed, but must first be discussed with a trial medical expert * pregnancy or risk of pregnancy in females of child bearing potential

Keywords: antiretroviral therapy child hiv-1