Therapeutic Drug Monitoring in HIV-Infected Children Starting a New Anti-Retroviral Regime.

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR316
• Date of registration: 09/09/2005
• Primary sponsor: Paediatric European Network for Treatment of AIDS (PENTA)
• Public title: Therapeutic Drug Monitoring in HIV-Infected Children Starting a New Anti-Retroviral Regime.
• Scientific title: An open, randomised, controlled trial in HIV-1 infected children starting or switching to a new antiretroviral therapy (ART) regimen. Findings to what level therapeutic drug monitoring is needed related to achieve full viral suppression and avoidance of resistence long term. - N/A
• Date of first enrolment: 15/10/2004
• Target sample size: 166
• Recruitment status: other
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=316
• Study type: intervention
• Study design: Randomised: Yes; Masking: Double; Control: Active; Group: Parallel; Type: 2 or more arms, randomized

Countries of recruitment

The Netherlands

Contacts

• Name: Ronald Groot, de

• Name: Diana Gibb

Key inclusion & exclusion criteria

Inclusion criteria: 1. Confirmed HIV-infected, i.e. positive plasma HIV-1 RNA or DNA test on two consecutive occasions (for children less than 18 months old), or positive HIV serology (for children aged 18 months and older) aged one month to 17 years inclusive;

2. Parents/guardians, and children where appropriate, are willing and able to give informed consent;

3. Plasma HIV-1 RNA viral load ³ 1000 copies/ml;

4. Pre-treated children, including children who have received antiretroviral therapy only as prophylaxis to reduce mother to child transmission, who are prepared to wait for the results of a resistance test before starting new therapy;

5. Starting antiretroviral therapy or switching to a new antiretroviral regimen considered likely to be highly active according to the results of a local resistance test, and containing either a PI or NNRTI or both; that is with:

a. Either 3 or more active drugs including a PI and/or NNRTI;

b. Or 2 active drugs: a boosted PI and an NNRTI.
Exclusion criteria: Grade 3 or 4 creatinine or liver function tests.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Human immunodeficiency virus (HIV)

Intervention(s)

Children randomised to group 1 will receive ?maximal TDM?. A full pharmacokinetic curve will be generated at week 4 (and repeated at 48 weeks) involving observed dosing and a day admission with repeat pharmacokinetic sampling (5 samples over 8 hours (18 hours for once daily NNRTIs).

If the full curve shows that the observed dose was inadequate compared against population PK data, the dose will be revised by the PK investigator and the full curve will be repeated 8-weekly until the dose is correct. (It is estimated that 30% of children will require a repeat curve.) Subsequent follow-up TDM samples will be taken with routine blood in the clinic (after unobserved but reported intake at least 4 hours previously) and will be used to monitor adherence, assess the likelihood of drug interactions and to check for toxicity.
Children randomised to group 2 will receive ?minimal TDM?. The week 4 single TDM sample will be taken at least 4 hours after reported but unobserved intake and will be used to check for adequate dosing against population PK data. The dose can be revised as advised by the PK investigator and the single TDM sample will be repeated 8-weekly until the dose is correct. Subsequent follow-up TDM samples will be taken with routine blood in the clinic (after unobserved but reported intake) and will be used to monitor adherence, assess the likelihood of drug interactions and control for toxicity, as for the maximal TDM group above.

Children randomised to group 3 will not receive any TDM results. All TDM samples will be analysed retrospectively at the end of the trial.

The week 4 single TDM sample will be taken at least 4 hours after reported but unobserved intake, to match samples taken from the ?minimal? TDM group, and will be used to check for adequate dosing against population PK data at the end of the trial.

All subsequent scheduled TDM samples will be taken at least four hours after unobserved but reported intake with routin

Primary Outcome(s)

The effect of the TDM strategies on the viral load in terms of change from baseline (start or switch of therapy) to 96 weeks.

Secondary Outcome(s)

1. The proportion of children who ever achieve plasma HIV-1 RNA <50 copies/ml, and who subsequently maintain plasma HIV-1 RNA <50 copies/ml to 96 weeks;

2. Toxicity and tolerability of HAART;

3. Adherence to HAART as assessed by caregiver completed questionnaire and CORALs;

4. Progression to new AIDS defining event or death;

5. Number of switches in antiretroviral therapy;

6. The development of new genotypic resistance mutations by 96 weeks;

7. Change in CD4 % and CD4 count from baseline to 96 weeks;

8. Number of children in target area for pharmacokinetic parameters after 12 weeks.

Secondary ID(s)

N/A

Source(s) of Monetary Support

GlaxoSmithKline, Paediatric European Network for Treatment of AIDS (PENTA)