FUNDING ORGANIZATION	RESEARCH ORGANIZATION	PROGRAM	DIRECTOR	CITY	COUNTRY	ABSTRACT
	MRC	UNIVERSITY OF ZIMBABWE	A RANDOMISED TRIAL OF MONITORING PRACTICE AND PULSE ANTIRETROVIRAL THERAPY IN AFRICAN CHILDREN WITH HIV INFECTION (ARROW TRIAL)	NATHOO, K	HARARE	ZIMBABWE	View
Junior DART is a randomised open-label trial enrolling 1200 African HIV-infected children, aged 6 months to 18 years, with an adult carer in the DART (Development of AntiRetroviral Therapy) trial which has enrolled 2000 of 3000 adults in Uganda (2 sites) and Zimbabwe (1 site). Junior DART will take place in the same sites and the 2 trial teams will work closely together. Junior DART will have two major randomisations: to clinical monitoring only (CMO) versus laboratory and clinical monitoring (LCM); and to intermittent (planned treatment interruptions, PTI) versus continuous ART. In a further randomised substudy, 3 regimen strategies for initiating ART will be compared in terms of HIV RNA viral load response. Eligible children should have paediatric WHO Stage 2 or 3 disease, and CD4 percent 20% for children 2 years, 15% for children 2-11 years, or CD4 count 200 cells/mm3 for those aged 12-18 years. It is expected that at least 750 children randomised to CMO versus LCM will be 2 years and have achieved a sufficient increase in CD4 (CD4 ?20% for 2-11 years and CD4 250 cells/mm3 for 12-18 years) by 48 or 72 weeks to be eligible for the second randomisation to PTI versus continuous ART. This will only open after a non-randomised pilot study of PTIs in 100 children satisfying these threshold criteria has been completed (with all children having monthly CD4 measurements) and the DSMC and Trial Steering Committee have assessed the safety of the proposed PTI strategy. Recruitment into the trial will take place over one year with minimum follow-up of 4 years. First and second-line ART will be available for all children (for up to five years). The decision to change to second-line ART will be based on clinical criteria alone for the CMO arm and on clinical plus laboratory criteria for the LCM arm. Issues of after-trial ART are being negotiated with governments in the same way as for adult DART. The primary efficacy endpoint will be progression to a new paediatric WHO stage 3 (AIDS) event or death in children under 13 years, or adult WHO stage 4 disease for those 13 years and older. The primary outcome for the randomised substudy will be change in HIV RNA from baseline to 48 weeks, performed retrospectively on stored plasma samples.