The ARROW (AntiRetroviral Research fOr Watoto) protocol describes an open-label randomised trial evaluating two strategic approaches for management of antiretroviral therapy (ART) in 1200 symptomatic HIV infected infants and children in Uganda and Zimbabwe.
The first strategy compares clinically driven monitoring (CDM) with laboratory plus clinical monitoring (LCM). The second approach compares a continuous first line ART three drug two class regimen, comprising two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) plus one Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), with induction with four drugs (two classes) followed by maintenance with three drugs.
A total of 1200 children from 4 African sites (3 in Uganda, 1 in Zimbabwe) will be enrolled over 12-18 months and followed for 31/2-5 years. In both CDM and LCM arms, children will have haematology and liver function tests performed routinely but the results will only be returned to clinicians caring for children in the CDM arm if requested by the treating physician for clinical reasons or indicative of a grade 4 adverse event. The exception will be return of haemoglobin results on all children at week 8. CD4 counts will be performed both in CDM and LCM arms with results not returned to physicians in the CDM arm but monitored independently by the Data Monitoring Committee (DMC).
The second randomisation, to ART strategies for first-line therapy, will also take place at enrolment. All children will receive two NRTIs - abacavir (ABC) and lamivudine (3TC) - plus an NNRTI (either efavirenz [EFV] or nevirapine [NVP]). The control arm (arm A) will continue with this 3-drug ART regimen for the duration of first-line therapy. The induction maintenance arms (Arms B and C) will receive a fourth drug, the NRTI zidovudine (ZDV), for the first 36 weeks. After 36 weeks, children in Arm B will stop taking ZDV and children in Arm C will stop taking NNRTI (i.e. both arms will reduce to 3 drugs) for the remainder of their first-line ART. See trial schema.
The primary efficacy endpoint will be progression to a new paediatric WHO HIV stage 4 disease event or death.