With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.
Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (two consecutive unsuppressed viral loads with the second being >1,000 copies/ml, after ≥24 weeks of therapy) and switch to second-line. Cox proportional hazards models stratified by program were used to determine predictors of these outcomes.
The 3-year probability of virologic failure among 5485 children was 19.3% (95%CI: 17.6–21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared to efavirenz), and exposure to prevention of mother to child transmission regimens were independently associated with failure (adjusted hazard ratios (95%CI): 1.77(1.11–2.83), 2.39(1.57–3.64) and 1.40(1.02–1.92) respectively). Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (IQR) months between failure and switch was 5.7(2.9–11.0).
Triple ART based on nevirapine or ritonavir as a single protease inhibitor appears to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.
Keywords: antiretroviral therapy, virologic failure, children, second-line therapy, resource-limited setting