Therapeutic drug monitoring (TDM) in human immunodeficiency virus (HIV)-infected children starting a new anti-retroviral regime

ISRCTN	ISRCTN33191903
DOI	https://doi.org/10.1186/ISRCTN33191903
Protocol serial number	PENTA 14
Sponsor	The Paediatric European Network for the treatment of AIDS (PENTA - Chair Dr Carlo Giaquinto)
Funder	European Union (EU) - grant (ref: QLK2-2000-00150)

Submission date: 11/07/2003
Registration date: 25/02/2004
Last edited: 10/02/2011

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Carlo Giaquinto
Scientific

Clinica Pediatrica
Universita di Padova
Via Giustiniani 3
Padova
35128
Italy

Phone	+39 (0)49 821 3563
Email	carlog@child.pedi.unipd.it

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	PENTA 14
Study objectives	1. To assess the effect of different levels of Therapeutic drug monitoring (TDM) compared with no TDM on plasma human immunodeficiency virus-1 ribonucleic acid (HIV-1 RNA) response in children starting or switching to a new highly active antiretroviral therapy (HAART) regimen including a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) 2. To generate age-related population pharmacokinetic models for PIs and NNRTIs used in children 3. To describe the impact of a didactic adherence support tool for children taking HAART, which will be offered to centres participating in the trial
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Paediatric HIV
Intervention	Full five point annual pharmacokinetic (PK) curve versus single sample PK versus no intervention. All children will receive additional adherence support.
Intervention type	Other
Primary outcome measure(s)	The effect of the TDM strategies on viral load in terms of change in plasma HIV-1 RNA copies/ml from baseline to 96 weeks
Key secondary outcome measure(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 week 96 8. Number of children in the target area for pharmacokinetic parameters after 12 weeks 9. Number of dosage adjustments based on pharmacokinetic parameters after 48 weeks
Completion date	01/11/2007
Reason abandoned (if study stopped)	Recruitment problems which were caused mainly by TDM being accepted as routine practice.

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	1 Month
Upper age limit	17 Years
Sex	All
Target sample size at registration	166
Key inclusion criteria	1. Confirmed HIV-infected, i.e. positive plasma HIV-1 RNA or deoxyribonucleic acid (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 = 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 at least two active drugs, one being a PI or NNRTI (active means not fully resistant)
Key exclusion criteria	Grade 3 or 4 creatinine or liver function tests
Date of first enrolment	01/07/2004
Date of final enrolment	01/11/2007

Locations

Countries of recruitment

United Kingdom
Germany
Italy
Netherlands

Study participating centre

Clinica Pediatrica

Padova
35128
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Study website	Study website	11/11/2025	11/11/2025	No	Yes