Infectious disease - Paediatric HIV Infections and Infestations Human immunodeficiency virus
Conditions
Interventions
Children will already be taking lopinavir/ritonavir. Dosage should be adjusted to the FDA approved daily doses (based on weight bands) as part of their combined ART. Children will be randomised to tak
Sponsors
The PENTA Foundation (Italy)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged less than 18 years (up to 18th birthday) with confirmed HIV-1 infection, either sex 2. Weight greater than or equal to 15 kg 3. Able to swallow tablets 4. Stable (i.e. CD4 not declining) on a combination antiretroviral regimen that has included lopinavir/ritonavir for at least 24 weeks, and expected to stay on the same regimen for the next 48 weeks 5. 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; if participating in the PK study, be willing at the screening visit to change to lopinavir/ritonavir half strength formulation tablets (100/25 mg) only, dosed twice-daily and change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary 6. Viral suppression (HIV-1 ribonucleic acid [RNA] less than 50 copies/ml) for at least the prior 24 weeks (minimum of two measurements) 7. 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 8. Parents/carers and children, where applicable, give informed written consent
Exclusion criteria
Exclusion criteria: 1. Children on an antiretroviral regimen that includes a non-nucleoside reverse transcriptase inhibitor (NNRTI), fosamprenavir or nelfinavir 2. Children who have previously failed virologically on a protease inhibitor (PI)-containing regimen (where virological failure is defined as two successive HIV-1 ribonucleic acid [RNA] results greater than 1000 copies/ml [confirmed] more than 24 weeks after starting highly active anti-retroviral therapy [HAART], i.e changes for toxicity are not counted as failure) 3. Intercurrent illness 4. Abnormal renal or liver function (grade 3 or above) 5. Receiving concomitant therapy except prophylactic antibiotics 6. Pregnancy or risk of pregnancy in females of child-bearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. HIV-1 RNA greater than or equal to 400 copies/ml (confirmed) at any of week 4, 8, 12, 24, 36 or 48 2. Area under curve (AUC), Cmin and Cmax values of lopinavir after twice-daily dosing compared to historical adult and paediatric data 3. AUC, Cmin and Cmax values of lopinavir after once-daily and twice-daily dosing (in the same children) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. HIV-1 RNA less than 400/less than 50 copies/ml at 24 and 48 weeks 2. HIV-1 RNA greater than or equal to 50 and less than 400 copies/ml at any of week 4, 8, 12, 24, 36 or 48 3. Number of HIV mutations present at week 4, 8, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the trial 4. Change in CD4 (absolute and percentage) from baseline to 24 and 48 weeks 5. Change in ART (defined as any change from the ART regimen at randomisation) 6. ART-related grade 3 or 4 clinical and laboratory adverse events 7. New Centers for Disease Control and Prevention (CDC) stage C diagnosis or death 8. Cchild and family acceptability of and adherence to twice-daily lopinavir/ritonavir 100/25 mg tablets dosed on body weight, over 48 weeks as assessed by patient/carer completed questionnaires 9. Child and family acceptability of and adherence to once-daily compared to twice-daily dosing of lopinavir/ritonavir tablets, over 48 weeks as assessed by patient/carer completed questionnaires | — |
Countries
Austria, Belgium, Brazil, Denmark, Germany, Ireland, Italy, Netherlands, Poland, Spain, Sweden, Thailand, United Kingdom
Outcome results
None listed