Once vs twice-daily abacavir and lamivudine in African children.

BACKGROUND: Antiretroviral therapy (ART) adherence is critical for successful HIV treatment outcomes. Once-daily dosing could improve adherence. Plasma concentrations of once-daily vs twice-daily abacavir + lamivudine are bioequivalent in children, but no randomized trial has compared virological outcomes. METHODS: Children taking abacavir + lamivudine-containing first-line regimens twice daily for more than 36 weeks in the ARROW trial (NCT02028676, ISRCTN24791884) were randomized to continue twice-daily vs move to once-daily abacavir + lamivudine (open-label). Co-primary outcomes were viral load suppression at week 48 (12% noninferiority margin, measured retrospectively) and lamivudine or abacavir-related grade 3/4 adverse events. RESULTS: Six hundred and sixty-nine children (median 5 years, range 1-16) were randomized 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 viral load less than 80 copies/ml [difference -1.6% (95% confidence interval -8.4,+5.2%) P = 0.65]; 79% twice daily vs 78% once daily had viral load less than 400 copies/ml (P = 0.76) (week 96 results similar). One grade 3/4 adverse event 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 randomized groups in postbaseline drug-resistance mutations or drug-susceptibility; WHO 3/4 events; ART-modifying, grade 3/4 or serious adverse events; CD4% or weight-for-age/height-for-age (all P > 0.15). CONCLUSION: Once-daily abacavir + lamivudine was noninferior to twice daily in viral load 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.

Young HIV-infected children and their adult caregivers prefer tablets to syrup antiretroviral medications in Africa.

BACKGROUND: Provision of anti-retroviral therapy (ART) for HIV-infected children is complicated using syrup formulations, which are costlier than tablets, harder to transport and store and difficult for health-workers to prescribe and caregivers to administer. Dispersible/crushable tablets may be more appropriate. We studied the acceptability of syrups and scored tablets among young children who used both in the AntiRetroviral Research fOr Watoto (ARROW) trial. METHODS: ARROW is an ongoing randomized trial of paediatric ART monitoring and treatment strategies in 1206 children in Uganda and Zimbabwe. 405 children initially received syrups of combination ART including Nevirapine, Zidovudine, Abacavir and Lamivudine before changing, when reaching the 12-<15 kg weightband, to scored adult-dose tablets prescribed according to WHO weightband tables. Caregiver expectations and experiences were collected in questionnaires at their last visit on syrups and after 8 and 24 weeks on tablets. RESULTS: Questionnaires were completed by caregivers of 267 children (median age 2.9 years (IQR 2.5, 3.4)). At last visit on syrups, 79% caregivers reported problems with syrups, mostly related to number, weight, transportation and conspicuousness of bottles. Difficulties taking tablets were expected by 127(48%) caregivers; however, after 8 and 24 weeks, only 26% and 18% reported their children had problems with tablets and no problems were reported with transportation/conspicuousness. Taste, swallowing or vomiting were reported as problems 'sometimes/often' for 14%, 9%, 22% children on syrups and 16%, 9%, 8% on tablets. At last visit on syrups, 74% caregivers expected to prefer tablets but only 27% thought their child would. After 8/24 weeks, 94%/97% caregivers preferred tablets and 57%/59% reported their child did. CONCLUSIONS: Most children at about 3 years can take tablets; caregivers and children themselves generally prefer tablets to liquid formulations of HIV medications above this age. Preferences of caregivers and children should be considered when designing and licensing paediatric drug formulations.