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

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.

Association between age at antiretroviral therapy initiation and 24-month immune response in West-African HIV-infected children.

OBJECTIVE: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4 cell response in West African HIV-infected children. METHODS: All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4 cell count measurements, including one at ART initiation (baseline) were included. CD4 cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4 cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model compared immune recovery for age within 24 months post-ART. RESULTS: Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4 cell gains compared with children less than 2 years, the reference group (P<0.001). However, by 24 months, we observed higher CD4 cell gain in children who initiated ART between 3 and 4 years compared with those less than 2 years (P<0.001). The 24-month CD4 cell gain was also strongest in immunodeficient children at baseline. Among these children, 75% reached immune recovery: 12-month rates were significantly highest in all those aged 2-5 years at ART initiation compared with those less than 2 years. Beyond 12 months on ART, immune recovery was significantly lower in children initiated more than 5 years (adjusted hazard ratio: 0.69, 95% confidence interval: 0.56-0.86). CONCLUSION: These results suggest that both the initiation of ART at the earliest age less than 5 years and before any severe immunodeficiency is needed for improving 24-month immune recovery on ART.