Musiime, V;
Kasirye, P;
Naidoo-James, B;
Nahirya-Ntege, P;
Mhute, T;
Cook, A;
Mugarura, L;
... Walker, AS; + view all
(2016)
Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial.
AIDS
, 30
(11)
pp. 1761-1770.
10.1097/QAD.0000000000001116.
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Abstract
Background: ART adherence is critical for successful HIV treatment outcomes. Once-daily dosing could improve adherence. Plasma concentrations of once- vs twice-daily abacavir+lamivudine are bioequivalent in children, but no randomised trial has compared virological outcomes. / Methods: Children taking abacavir+lamivudine-containing first-line regimens twice-daily for >36 weeks in the ARROW trial (NCT02028676,ISRCTN24791884) were randomised to continue twice-daily versus move to once-daily abacavir+lamivudine (open-label). Co-primary outcomes were viral load (VL) suppression at week-48 (12% non-inferiority margin, measured retrospectively) and lamivudine or abacavir-related grade 3/4 adverse events (AEs). / Results: 669 children (median 5 years, range 1-16) were randomised to twice-daily (n=333) vs once-daily (n=336) after median 1.8 years on twice-daily abacavir+lamivudine-containing first-line ART. Children were followed for median 114 weeks. At week-48, 242/331 (73%) twice-daily vs 236/330 (72%) once-daily had VL<80c/ml (difference -1.6% [95% CI -8.4%,+5.2%] p=0.65); 79% twice-daily vs 78% once-daily had VL<400c/ml (p=0.76) (week-96 results similar). One grade 3/4 AE was judged uncertainly related to abacavir+lamivudine (hepatitis; once-daily). At week-48, 9% twice-daily vs 10% once-daily reported missing one or more ART pills in the last 4 weeks (p=0.74), and 8% vs 8% at week-96 (p=0.90). Carers strongly preferred once-daily dosing. There was no difference between randomised groups in post-baseline drug-resistance mutations or drug-susceptibility; WHO 3/4 events; ART-modifying, grade 3/4 or serious AEs; CD4% or weight/height-for-age (all p>0.15). / Conclusions: Once-daily abacavir+lamivudine was non-inferior to twice-daily in VL suppression, with similar resistance, adherence, clinical, immunological and safety outcomes. Abacavir+lamivudine provides the first once-daily nucleoside backbone across childhood that can be used to simplify ART.
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