Long-term Outcome of Children Receiving Antiretroviral Treatment in Rural South Africa: Substantial Virologic Failure on First-line Treatment

Background: Long-term (>12 months follow-up) virologic data of children receiving antiretroviral therapy (ART) in Sub-Saharan Africa are limited. Data from rural areas are especially scarce. The aim of this study was to evaluate the long-term virologic outcome of a pediatric cohort in rural South Africa.

Methods: We performed a retrospective, observational cohort study, including children who initiated ART at least 1 year before data-analysis. Regular monitoring, including HIV-RNA testing, was performed. Genotypic resistance testing was done for children with virologic failure (HIV-RNA >1000 copies/mL). Logistic regression analysis was used to determine predictors of virologic failure.

Results: A total of 101 children were included. Median duration since beginning ART was 31 months. Overall patient retention-rate was 76% (77/101), with early mortality being the main cause of attrition (13/24, 54%). Initial immunologic and virologic responses were excellent. However, 38% (31/81) of children subsequently experienced virologic failure. Correlation between virologic failure and immunologic decline was nearly absent. At the time of failure, multiple non-nucleoside reverse transcription inhibitor-associated mutations were observed in 52% (12/23) of children. No definite predictors of virologic failure could be determined.

Conclusions: ART provides significant benefits for children in this rural African setting, but the finding that a large proportion of children had virologic failure and developed major drug-resistance mutations on first-line ART is worrying. Causes of failure need to be analyzed and effective prevention strategies are needed. Because of the lack of a correlation between immunologic and virologic failure, treatment failure generally stays unnoticed in settings where HIV-RNA testing is not available.