Abstract
BACKGROUND: Treatment failure of antiretroviral therapy (ART) has become an increasingly global health issue. In Ethiopia, prior studies on ART failure rates have focused primarily on adults in hospital settings with varying definitions of treatment failure, leaving pediatric data scarce. Thus, this study aimed to determine the incidence rate of treatment failure and its predictors among children enrolled in first-line ART in Jimma, Ethiopia. METHODS: A retrospective cohort study was conducted at health facilities in Jimma, Ethiopia. A total of 312 children who were enrolled in first-line ART from January 2015 to December 2024 were selected via systematic random sampling. The data were retrieved by reviewing the child’s medical records and analyzed using Stata software. We utilized a multivariable Cox regression model to identify predictors of treatment failure and adjusted hazards ratio (AHR) with 95% confidence intervals (CI) to measure the associations. A p-value < 0.05 was used to declare statistically significant associations. RESULTS: The proportion of pediatric first-line ART failure in this study was 15.71% (95% CI: 11.57, 19.85), with an overall incidence density of 2.07 per 1,000 person-months (95% CI: 1.56, 2.74). The predictors significantly associated with ART failure were underweight (AHR = 3.95, 95% CI: 1.63, 9.57), anemia (AHR = 3.01, 95% CI: 1.51, 6.01), delayed ART initiation (AHR = 3.46, 95% CI: 1.32, 9.06), fair or poor adherence (AHR = 11.36, 95% CI: 5.22, 24.73), and advanced HIV disease (AHR = 2.49, 95% CI: 1.34, 4.66). Conversely, caregivers with positive serostatus (AHR = 0.191, 95% CI: 0.078, 0.46) and children aged 10–14 years (AHR = 0.064, 95% CI: 0.023, 0.17) had a significantly reduced risk of failure compared with their counterparts. CONCLUSION: First-line ART failure among children remains high, rendering achieving the nation’s HIV-free generation target difficult. To improve pediatric HIV outcomes in Ethiopia, future interventions should focus on rapid ART initiation, adherence counseling, nutritional support, and early anemia screening and management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-026-06674-0.