Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial
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 ou...
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| Materiálatiipa: | Journal article |
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Lippincott, Williams and Wilkins
2016
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| _version_ | 1826302701976158208 |
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| author | Musiime, V Kasirye, P Naidoo-James, B Nahirya-Ntege, P Mhute, T Cook, A Mugarura, L Munjoma, M Thoofer, N Ndashimye, E Nankya, I Spyer, M Thomason, M Snowden, W Gibb, D Walker, A ARROW Trial Team |
| author_facet | Musiime, V Kasirye, P Naidoo-James, B Nahirya-Ntege, P Mhute, T Cook, A Mugarura, L Munjoma, M Thoofer, N Ndashimye, E Nankya, I Spyer, M Thomason, M Snowden, W Gibb, D Walker, A ARROW Trial Team |
| author_sort | Musiime, V |
| collection | OXFORD |
| description | 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. <br/> 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. <br/> 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). <br/> 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. |
| first_indexed | 2024-03-07T05:51:33Z |
| format | Journal article |
| id | oxford-uuid:e90f7c66-1701-43bb-9f99-df9023a9d366 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:51:33Z |
| publishDate | 2016 |
| publisher | Lippincott, Williams and Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:e90f7c66-1701-43bb-9f99-df9023a9d3662022-03-27T10:51:31ZOnce- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW TrialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e90f7c66-1701-43bb-9f99-df9023a9d366Symplectic Elements at OxfordLippincott, Williams and Wilkins2016Musiime, VKasirye, PNaidoo-James, BNahirya-Ntege, PMhute, TCook, AMugarura, LMunjoma, MThoofer, NNdashimye, ENankya, ISpyer, MThomason, MSnowden, WGibb, DWalker, AARROW Trial TeamBackground: 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. <br/> 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. <br/> 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). <br/> 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. |
| spellingShingle | Musiime, V Kasirye, P Naidoo-James, B Nahirya-Ntege, P Mhute, T Cook, A Mugarura, L Munjoma, M Thoofer, N Ndashimye, E Nankya, I Spyer, M Thomason, M Snowden, W Gibb, D Walker, A ARROW Trial Team Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial |
| title | Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial |
| title_full | Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial |
| title_fullStr | Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial |
| title_full_unstemmed | Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial |
| title_short | Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial |
| title_sort | once versus twice daily abacavir and lamivudine in african children the randomised controlled arrow trial |
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