Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

AIDS. 2015 Jul 31;29(12):1527-36. doi: 10.1097/QAD.0000000000000707.

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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Africa, Western
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • CD4 Lymphocyte Count
  • Child
  • Child, Preschool
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Incidence
  • Male
  • Risk Factors
  • Time Factors
  • Treatment Failure
  • Viral Load

Substances

  • Anti-Retroviral Agents