Real-world effectiveness of antiretroviral backbone regimens on viral suppression in pediatric and adolescent HIV care: a six-year cohort study from Uganda

Background Optimizing nucleoside reverse transcriptase inhibitor (NRTI) backbones is vital for pediatric and adolescent HIV treatment, yet real-world comparative evidence is limited. This study assessed backbone regimen effectiveness and factors influencing viral suppression (VLS) in Uganda. Methods We conducted a retrospective cohort of 1033 children and adolescents (≤19 years) receiving HIV care in Uganda (2018–2023). Participants received Tenofovir Disoproxil Fumarate (TDF, 57.3%), Abacavir (ABC, 32.7%), or zidovudine (AZT, 10.0%). Viral load (VL) suppression was classified as suppressed (≤200 copies/mL), low-level viremia (201–999 copies/mL), and high-level viremia (≥1000 copies/mL). Outcomes were compared by χ 2 tests, and mixed-effects logistic regression identified factors associated with non-suppression over time. Findings Overall VLS was 83.5%. VLS was highest among TDF recipients (84.8%), followed by ABC (82.8%), and lowest with AZT (78.6%; p=0.313). AZT recipients had the highest high-level viremia (19.4%) and greater odds of non-suppression compared with ABC (adjusted odds ratio [aOR] 2.02, 95% CI 1.20–3.40; p=0.008). TDF was associated with lower odds of non-suppression in bivariable analysis (OR 0.71, 95% CI 0.53–0.95; p=0.023 but was not significant after adjustment (p = 0.748). Increasing age reduced the odds of non-suppression by 8% per year (aOR 0.92, 95% CI 0.86–0.98; p=0.006), while male sex increased odds of non-suppression (aOR 1.36, 95% CI 1.03–1.81; p=0.033). Later VL testing time points were linked to improved suppression (aOR 0.95, 95% CI 0.91–1.00; p=0.037). Interpretation Overall VLS exceeded 80% but fell short of the UNAIDS 95% target. TDF-backbones had the highest success, AZT the lowest. Younger age and male sex predicted poorer outcomes. These results highlight the need for optimized regimens, targeted adherence support, and strengthened programs to improve pediatric and adolescent HIV care. Funding National Institute for Health and Care Research (NIHR), United Kingdom through the Royal Society for Tropical Medicine and Hygiene Early Career Grants.