Antiretroviral research for Watoto

ISRCTN	ISRCTN24791884
DOI	https://doi.org/10.1186/ISRCTN24791884
Protocol serial number	G0300400
Sponsor	Medical Research Council (UK)
Funders	Medical Research Council (MRC) (UK) (ref: G0300400), Department for International Development

Submission date: 19/04/2006
Registration date: 09/06/2006
Last edited: 19/07/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=6

Contact information

Prof Diana Gibb
Scientific

Clinical Trials Unit, Medical Research Council
222 Euston Road
London
NW1 2DA
United Kingdom

Phone	+44 (0)20 7670 4709
Email	d.gibb@ctu.mrc.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised trial of monitoring practice and induction maintenance drug regimens
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Antiretroviral research for Watoto
Study acronym	ARROW
Study objectives	The key objectives are to determine: 1. Will clinically driven monitoring (CDM) have a similar outcome in terms of disease progression or death as routine laboratory and clinical monitoring (LCM) for toxicity (haematology/biochemistry) and efficacy (CD4)? 2. Will induction with four drugs (2 antiretroviral therapy [ART] classes) followed by maintenance with three drugs after 36 weeks be more effective than a continuous non-nucleoside reverse transcriptase inhibitors (NNRTI)-based triple drug regimen in terms of CD4 and clinical outcome? In addition there will be a sub-study to evaluate a visual analogue scale for assessing 28-day adherence to ART, by comparing with 3-day recall, pill and bottle counts (including unannounced checks at home). This will be performed on a subset of children enrolled in the trial.
Ethics approval(s)	1. University College London (UCL) (UK), 25/05/2006, ref: 0701/001 2. Ugandan National Council for Science & Technology (UNCST) (Uganda), 16/02/2006 3. JCRC IRB/REC & Uganda Virus Institute Science and Ethics Committee (Uganda), 14/07/2006 4. Baylor College of Medicine (Uganda), approved on 12 October 2006 (Uganda), 12/10/2006, ref: H-19616 5. Medical Research Council of Zimbabwe (MRCZ) (Zimbabwe), 05/04/2007, ref: MRC/A/1321 6. Medicines Control Authority of Zimbabwe (MCAZ) (Zimbabwe), 04/05/2007, ref: B/279/5/52/2007
Health condition(s) or problem(s) studied	Human immunodeficiency virus
Intervention	First randomisation is to CDM or LCM (1200 children). Second randomisation is to either continuous or induction-maintenance ART strategies for first-line therapy. Children will be randomised immediately after their first randomisation to CDM or LCM.
Intervention type	Other
Primary outcome measure(s)	1. Monitoring practice (n = 1200): 1.1. Efficacy: progression to a new WHO stage 4 or death 1.2. Safety: any adverse events of grade 3 or 4, which are not HIV-related only 2. ART strategies for first-line therapy (n=1200): 2.1. Efficacy: progression to a new WHO stage 4 or death and change in CD4 percentage at 72 and 144 weeks 2.2. Safety: any adverse events of grade 3 or 4, which are not HIV-related only
Key secondary outcome measure(s)	No secondary outcome measures
Completion date	14/03/2012

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	17 Years
Sex	All
Target sample size at registration	1200
Key inclusion criteria	1. Children should have an adult carer in the household who is either: 1.1. Participating in the DART trial (ISRCTN13968779) or 1.2. Being treated with ART or 1.3. HIV positive but not yet needing treatment but with access to a treatment program when ART is required or 1.4. HIV negative 2. Parents or guardians, and children where appropriate according to age and knowledge of HIV status, must be willing and able to give informed consent for randomisation to clinically driven monitoring (CDM) or laboratory and clinical monitoring (LCM) and to first-line ART strategy 3. Participants must have a confirmed and documented diagnosis of HIV-1 infection 4. At entry participants should be aged: 4.1. 6 Months to 17 years among children and adolescents from DART households 4.2. 6 Months to 12 years among children in non-DART households 5. Participants must be ART naive (except for exposure to perinatal ART for the prevention of mother-to-child HIV transmission) 6. Participants must meet the criteria for requiring ART according to World Health Organization (WHO) stage and CD4 count or CD4 cell percent
Key exclusion criteria	1. Cannot, or unlikely to attend regularly 2. Likelihood of poor adherence 3. Presence of acute infection 4. In receipt of medication contraindicated by ART or on chemotherapy for malignancy 5. Laboratory abnormalities, which are a contraindication for the patient to start ART 6. Pregnant or breastfeeding
Date of first enrolment	02/10/2006
Date of final enrolment	14/03/2012

Locations

Countries of recruitment

United Kingdom
England
Uganda
Zimbabwe

Study participating centre

Clinical Trials Unit, Medical Research Council

London
NW1 2DA
United Kingdom

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?
Results article	results	20/04/2013		Yes	No
Results article	results	02/01/2014		Yes	No
Results article	results	17/07/2016		Yes	No
Results article	Sub study results		19/07/2021	Yes	No
Other publications	observational analyses	14/11/2017		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

15/11/2017: Publication reference added.
12/04/2016: Publication reference added.