title: Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation.
abstract: BACKGROUND
  We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa.
  
  
  METHODS
  We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric IeDEA clinical centres in five West-African countries. We estimated the incidence of switch (at least one a drug class change) within 24 months of ART and associated factors were identified in a multinomial logistic regression. Among children with clinical-immunological failure, we estimated the 24-month probability of switching to a second-line and associated factors, using competing risks. Children who switched to second-line ART following the withdrawal of nelfinavir in 2007 were excluded.
  
  
  RESULTS
  Overall, 2820 children initiated ART at a median age of 5 years; 144 (5%) were on nelfinavir. At 24-month post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months. Of these children, 21 (7%) switched to second-line after a median time of 21 weeks in failure. This was associated with older age [subdistribution hazard ratio (sHR) 1.21, 95% confidence interval (95% CI) 1.10-1.33] and longer time on ART (sHR 1.16, 95% CI 1.07-1.25).
  
  
  CONCLUSIONS
  Switches for clinical failure were rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes.
authors.affiliation: aInstitut de Santé Publique, d'Epidémiologie et de Développement, Université Bordeaux bInserm, Centre Inserm U897-Epidémiologie-Biostatistique, Bordeaux, France cCHU de Yopougon, Abidjan, Côte d'Ivoire dHopital Gabriel Toure, Bamako, Mali eIeDEA Regional Center, PACCI, CHU de Treichville fCentre pédiatrique de Prise en charge, de Recherche et de Formation (CePReF), Abidjan, Côte d'Ivoire gHôpital pédiatrique, CHU Charles de Gaulle, Ouagadougou, Burkina Faso hHôpital d'enfants Albert-Royer, Dakar, Sénégal iKorle Bu Hospital, Accra, Ghana jService pédiatrie CHU National, Cotonou, Benin. *See composition in Acknowledgements.
authors.forename: Sophie
authors.initials: S
authors.lastname: Desmonde
authors.forename: François T
authors.initials: FT
authors.lastname: Eboua
authors.forename: Karen
authors.initials: K
authors.lastname: Malateste
authors.forename: Fatoumata
authors.initials: F
authors.lastname: Dicko
authors.forename: Didier K
authors.initials: DK
authors.lastname: Ekouévi
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ngbeché
authors.forename: Fla
authors.initials: F
authors.lastname: Koueta
authors.forename: Haby Signate
authors.initials: HS
authors.lastname: Sy
authors.forename: Lorna
authors.initials: L
authors.lastname: Renner
authors.forename: Siriatou A
authors.initials: SA
authors.lastname: Koumakpai
authors.forename: Valeriane
authors.initials: V
authors.lastname: Leroy
mesh_terms: D000354:Africa, Western; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents