Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Prof Diana Gibb


Contact details

Clinical Trials Unit
Medical Research Council
222 Euston Road
United Kingdom
+44 (0)20 7670 4709

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title



Study hypothesis

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

Added as of 27/07/2007:
1. University College London (UCL) (UK), on 25/05/2006 (ref: 0701/001)
2. Ugandan National Council for Science & Technology (UNCST) (Uganda) on 16/02/2006
3. JCRC IRB/REC & Uganda Virus Institute Science and Ethics Committee (Uganda) on 14/07/2006
4. Baylor College of Medicine (Uganda), approved on 12 October 2006 (Uganda) on 12/10/2006 (ref: H-19616)
5. Medical Research Council of Zimbabwe (MRCZ) (Zimbabwe) on 05/04/2007 (ref: MRC/A/1321)
6. Medicines Control Authority of Zimbabwe (MCAZ) (Zimbabwe) on 04/05/2007 (ref: B/279/5/52/2007)

Study design

Randomised trial of monitoring practice and induction maintenance drug regimens

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet

Patient information can be found at:


Human immunodeficiency virus


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



Not Specified

Drug names

Primary outcome measures

The primary endpoints are:
1. Monitoring practice (n = 1200):
a. Efficacy: progression to a new WHO stage 4 or death
b. Safety: any adverse events of grade 3 or 4, which are not HIV-related only

2. ART strategies for first-line therapy (n=1200):
a. Efficacy: progression to a new WHO stage 4 or death and change in CD4 percentage at 72 and 144 weeks
b. Safety: any adverse events of grade 3 or 4, which are not HIV-related only

Secondary outcome measures

No secondary outcome measures

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Children should have an adult carer in the household who is either:
a. Participating in the DART trial (ISRCTN13968779) or
b. Being treated with ART or
c. HIV positive but not yet needing treatment but with access to a treatment program when ART is required or
d. 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:
a. 6 Months to 17 years among children and adolescents from DART households
b. 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

Participant type


Age group




Target number of participants


Participant 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 breast-feeding

Recruitment start date


Recruitment end date



Countries of recruitment

Uganda, Zimbabwe

Trial participating centre

Clinical Trials Unit, Medical Research Council
United Kingdom

Sponsor information


Medical Research Council (UK)

Sponsor details

Medical Research Council Centre
Stephenson House
158-160 North Gower Street
United Kingdom
+44 (0)20 7670 4625

Sponsor type

Research council



Funder type

Research council

Funder name

Medical Research Council (MRC) (UK) (ref: G0300400)

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


United Kingdom

Funder name

The Department for International Development (DFID) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in:
2014 results in:

Publication citations

  1. Results

    , Kekitiinwa A, Cook A, Nathoo K, Mugyenyi P, Nahirya-Ntege P, Bakeera-Kitaka S, Thomason M, Bwakura-Dangarembizi M, Musiime V, Munderi P, Naidoo-James B, Vhembo T, Tumusiime C, Katuramu R, Crawley J, Prendergast AJ, Musoke P, Walker AS, Gibb DM, Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trial., Lancet, 2013, 381, 9875, 1391-1403, doi: 10.1016/S0140-6736(12)62198-9.

  2. Results

    Bwakura-Dangarembizi M, Kendall L, Bakeera-Kitaka S, Nahirya-Ntege P, Keishanyu R, Nathoo K, Spyer MJ, Kekitiinwa A, Lutaakome J, Mhute T, Kasirye P, Munderi P, Musiime V, Gibb DM, Walker AS, Prendergast AJ, , A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa., N. Engl. J. Med., 2014, 370, 1, 41-53, doi: 10.1056/NEJMoa1214901.

Additional files

Editorial Notes