Antiretroviral Therapy in HIV-1 Infected Children
Conditions
Keywords
antiretroviral therapy, child, HIV-1
Brief 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.
Interventions
DRUGKaletra dosed once daily
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.
DRUGkaletra dosed twice daily
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.
Sponsors
Medical Research Council
ANRS, Emerging Infectious Diseases
PENTA Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). | week 48 | To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 Ribonucleic acid (RNA) ≥50 copies/ml (confirmed). |
| To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children | week 4 | Area under the curve (AUC), minimum observed plasma concentration (Cmin) and maximum observed plasma concentration (Cmax) values of lopinavir after once-daily and twice-daily dosing (in the same children) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml. | week 24 | To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA \<400/\<50 copies/ml. |
| Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets | week 48 | Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires |
Countries
Germany, Ireland, Netherlands, Thailand, United Kingdom
Outcome results
None listed