Details

Autor(en) / Beteiligte

• Musiime, Victor
• Kasirye, Philip
• Naidoo-James, Bethany
• Nahirya-Ntege, Patricia
• Mhute, Tawanda
• Cook, Adrian
• Mugarura, Lincoln
• Munjoma, Marshall
• Thoofer, Navdeep K
• Ndashimye, Emmanuel
• Nankya, Immaculate
• Spyer, Moira J
• Thomason, Margaret J
• Snowden, Wendy
• Gibb, Diana M
• Walker, Ann Sarah

Titel

Once vs twice-daily abacavir and lamivudine in African children

Ist Teil von

• AIDS (London), 2016-07, Vol.30 (11), p.1761-1770

Ort / Verlag

England: Copyright Wolters Kluwer Health, Inc

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.