Nasuuna, Esther MBabirye, LillianKigozi, JoanitaMuganzi, AlexIzudi, Jonathan2026-03-052026-03-052026-02-27Nasuuna, E. M., Babirye, L., Kigozi, J., Muganzi, A., & Izudi, J. (2026). Effectiveness of ART optimization on viral load suppression in children and adolescents with HIV in Uganda: A quasi-experimental study. Medicine, 105(9), e47862.1536-5964https://dir.muni.ac.ug/handle/20.500.12260/931This study examines how optimizing antiretroviral therapy (ART) affects viral load suppression among children and adolescents living with HIV in Uganda, bringing attention to the human realities behind clinical outcomes. By centering the experiences of young people and their families, the research reveals both the successes and ongoing challenges in fully implementing ART guidelines in public HIV clinics. Gaps in compliance with eligibility rules can hinder treatment success, underscoring the need for more responsive health systems and targeted support for vulnerable youth. These findings offer practical evidence to improve HIV treatment programs, strengthen adherence to clinical guidelines, and better support children and adolescents in their fight against HIV. The research advances SDG 3 (Good Health and Well-Being) by promoting effective disease control, SDG 10 (Reduced Inequalities) by focusing on the needs of vulnerable populations, and SDG 17 (Partnerships for the Goals) through enhanced coordination in healthcare delivery. Aligned with Uganda’s National Development Plan IV, this work emphasizes the importance of robust health systems and quality HIV care as foundations for healthier, more resilient communities.Uganda implemented the antiretroviral therapy (ART) optimization program in July 2019, based on an eligibility rule. ART optimization targeted individuals with prior viral load (VL) < 1000 copies/mL, while those with VL ≥ 1000 copies/mL continued with non-optimized regimens. We assessed the effectiveness of ART optimization on VL suppression among children and adolescents with HIV (CAWH) in Uganda. We also assessed the compliance of human immunodeficiency virus (HIV) clinics with the eligibility rule and its effect on ART optimization. Therefore, we designed a quasi-experimental study using data from 21 urban and rural HIV clinics. The exposure was ART optimization, defined as the initiation or transition of CAWH on dolutegravir or a protease inhibitor (boosted lopinavir). Children and adolescents with HIV on an optimized ART regimen formed the exposed group, while those on a non-optimized ART regimen comprised the nonexposed group. The primary outcome was VL suppression, defined by VL < 1000 copies/mL after ≥6 months of ART optimization. We assessed the effectiveness of ART optimization on VL suppression using 2-stage least squares instrumental variable regression due to imperfect compliance with the eligibility rule across the clinics. We also established the effectiveness of the eligibility rule on ART optimization for individuals just below and just above the cutoff. Sensitivity analysis was performed using a noncausal approach. We analyzed data from 2999 CAWH aged ≤19 years and found an overall VL suppression of 76.1% (2282/2999). We found that ART optimization showed a trend toward improved VL suppression (risk ratio [RR] 1.81, 95% CI: 0.79–4.14). However, compliance with the rule was only for 2.6% of the participants, and the rule did not improve ART optimization (RR 0.96, 95% CI: 0.88–1.05). Overall, ART optimization, guided by an eligibility rule, did not achieve the target of ≥95% VL suppression among CAWH across the 21 public HIV clinics in Uganda, partly due to low compliance with the rule, although it showed a trend toward improvement. Addressing context-specific biological, behavioral, social, and structural barriers is needed to optimize VL outcomes.enART optimizationChildren and adolescentsDolutegravirHIVUgandaViral load suppressionArticle