Viral suppression and adverse events following antiretroviral therapy optimization among children and adolescents in Uganda, 2018–2023

BACKGROUND: Despite widespread scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, evidence on the real-world impact of ART optimization; defined as any regimen transition intended to improve treatment outcomes; remains limited. Dolutegravir (DTG)-based regimen transitions are a key component, but other regimen switches are also critical strategies to enhance treatment outcomes. We evaluated regimen transitions, viral load trends, and safety outcomes among children and adolescents receiving HIV care at Mildmay Uganda Hospital (MUgH) before (2019) and after DTG rollout (2022). METHODS: We conducted a descriptive cross-sectional study of children and adolescents (≤ 19 years) (2018–2023), abstracting sociodemographic, clinical, and viral load data. Regimen transitions were classified into 11 groups; Abacavir (ABC)/Zidovudine (AZT) to DTG, DTG to DTG, Efavirenz (EFV) or Nevirapine (NVP) to DTG, EFV or NVP to Protease Inhibitor(PI), EFV or NVP to PI/DTG, and PI to DTG, PI, or PI/DTG based regimens. Viral load was classified as suppressed (≤ 200 copies/mL), low-level (201–999), or high-level viremia (≥ 1000). Descriptive statistics summarized baseline characteristics and regimen transitions. Overall Viral Load Suppression before (2019) and after optimization (2022) was compared using chi-square tests. Medical Dictionary classified adverse events for Regulatory Activities system organ class as percentages. RESULTS: One thousand thirty-six participants were included, with median age of 16 (12–18) years, at enrolment; 58.0% were ≥ 15 years and 52.7% female. Most (94.4%) resided in the Kampala Metropolitan Area and 95.2% initiated ART at MUgH. Following optimization, viral suppression improved across multiple transitions: EFV→DTG (81.3% to 88.0%), PI→DTG (52.3% to 86.1%), ABC/AZT→DTG (65.6% to 90.6%), and NVP→DTG (80.6% to 88.8%). EFV→PI maintained 80.0% suppression, whereas NVP→PI consistently showed 100% high-level viremia. Overall suppression increased from 67.9% to 81.7% (p < 0.001). Adverse events were predominantly Respiratory, thoracic and mediastinal disorders (49.2%), asymptomatic (16.5%), and skin disorders (12.2%), with other events occurring at ≤ 2%. CONCLUSION: ART optimization at MUgH enhanced viral suppression, particularly with dolutegravir-based regimens, while protease inhibitor transitions showed slower improvement. Persistent viremia and frequent respiratory events highlight the need for vigilant monitoring, adherence evaluation and support, and timely interventions to sustain long-term treatment success among children and adolescents living with HIV.