title: Once vs twice-daily abacavir and lamivudine in African children.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: aJoint Clinical Research Centre bDepartment of Paediatrics and Child Health, College of Health Sciences, Makerere University cBaylor-Uganda, Paediatric Infectious Diseases Clinic, Mulago Hospital, Kampala, Uganda dMedical Research Council (MRC) Clinical Trials Unit at University College London, London, UK eMedical Research Council/Uganda Research Unit on AIDS, Uganda Virus Research Institute, Entebbe, Uganda fUniversity of Zimbabwe, Harare, Zimbabwe gViiV HealthCare, Brentford, Middlesex, UK. *Diana M. Gibb and Ann Sarah Walker contributed equally to the writing of this manuscript.
authors.forename: Victor
authors.initials: V
authors.lastname: Musiime
authors.forename: Philip
authors.initials: P
authors.lastname: Kasirye
authors.forename: Bethany
authors.initials: B
authors.lastname: Naidoo-James
authors.forename: Patricia
authors.initials: P
authors.lastname: Nahirya-Ntege
authors.forename: Tawanda
authors.initials: T
authors.lastname: Mhute
authors.forename: Adrian
authors.initials: A
authors.lastname: Cook
authors.forename: Lincoln
authors.initials: L
authors.lastname: Mugarura
authors.forename: Marshall
authors.initials: M
authors.lastname: Munjoma
authors.forename: Navdeep K
authors.initials: NK
authors.lastname: Thoofer
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ndashimye
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.forename: Moira J
authors.initials: MJ
authors.lastname: Spyer
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Thomason
authors.forename: Wendy
authors.initials: W
authors.lastname: Snowden
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Ann Sarah
authors.initials: AS
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D000349:Africa; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D024882:Drug Resistance, Viral; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D000074243:Immune Reconstitution; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D055118:Medication Adherence; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D000099227:Abacavir