Virologic Failure and Second-Line Antiretroviral Therapy in Children in South Africa—The IeDEA Southern Africa Collaboration

Abstract

Background 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. Methods 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. Results 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). Conclusion 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.

Antiretroviral therapy for the management of HIV in children

“…[18] In the International epidemiologic Databases to Evaluate AIDS (IeDEA) cohort, children starting ART at around 3.5 years of age had a 20% rate of virological failure after 3 years. [30] The ARROW study confirmed this finding, with 83% of children on two NRTIs and an NNRTI having a viral load of <400 copies/mL after a median of 3.7 years on therapy. [17] Virological outcomes are equivalent to those in European or American children.…”

Magnitude and predictors of antiretroviral treatment failure among HIV-infected children in Fiche and Kuyu hospitals, Oromia region, Ethiopia: a retrospective cohort study

“…2010) and South Africa (Davis et al. 2011). Health care providers' lack of knowledge and skill to identify early evidence of treatment failure, frequent machine failure to do CD4, and viral load testing service to support diagnosis could be factors contributing for the delay.…”

Paediatric ART outcomes in a decentralised model of care in Cape Town, South Africa

“…Multiple logistic regression was performed to explore variables (including protease inhibitorcontaining ART and TB co-infection) that may be related to the risk of developing VF. [23] No variables were identified as having a confounding and effect-modifiying influence; however, baseline WHO clinical classification was so significantly predictive of VF that the variable was restricted from the model because of colinearity. Manual and automated model building were performed to create a best-fit model, which ultimately included ART initiation site and baseline VL log.…”