Low rates of switching to second-line treatment in children failing first-line ART

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

Desmonde S, Eboua FT, Malateste K, Dicko F, Ekouevi DK, Ngbeche S, Koueta F, Sy HS, Renner L, Koumakpai SA, Leroy V, IeDEA Pediatric West African Working Group. AIDS. 2015 Jul 31;29(12):1527-36. doi: 10.1097/QAD.0000000000000707.

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 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.

Abstract access  [1]

Editor’s notes: Data on the durability of first-line ART in children in low-income settings are limited. However, there is mounting evidence that children in facilities without routine viral load testing are less likely to be identified as failing on first-line therapy. This observational study by the IeDEA Paediatric West African working group illustrates that the rate of switch to second-line therapy in children on first-line treatment, monitored using clinical (with or without immunological) criteria, was low. Additionally, the majority of switches that did occur were due to ART availability issues, poor adherence and drug toxicity, rather than in response to clinically-defined treatment failure.  Some 12% of children failed first-line ART after a median of seven months, of whom only 0.8% switched to second-line ART. These findings highlight the missed opportunities and underscore the difficulties in identifying treatment failure in children within a context in which virologic monitoring is not yet available.

Health care delivery [4]
Africa [5]
Burkina Faso [6], Côte d'Ivoire [7], Ghana [8], Mali [9], Senegal [10]
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