Background: – Children and adolescents with HIV previously taking ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART) were recently programmatically transitioned to dolutegravir (DTG)-based ART in Lesotho, southern Africa. We investigated associated changes in treatment satisfaction and potential side effects. Methods: – This single-center prospective cohort study enrolled participants <18 years transitioned from LPV/r- to DTG-based ART during the national programmatic DTG rollout in 2022–2023. Virally suppressed participants ≥6 years able to handle a sleep diary and actigraphy were eligible for additional sleep monitoring. Enrollment occurred 2 weeks before (with actigraphy) or at (without actigraphy) transition with follow-up until 4 weeks post-transition. Co-primary endpoints were i) change in treatment satisfaction, using the HIV Treatment Satisfaction Questionnaire change version (HIVTSQc; Teen and Parent versions) at 4 weeks, and ii) difference in mean sleep period length over a two-week period before and after transition (only actigraphy participants). Secondary endpoints assessed treatment satisfaction status, gastrointestinal symptoms, depressive symptoms, and additional sleep measures. Results: – Among 245 participants with transition and 4-week data, 115 (47%) were female and median age was 11.1 (interquartile range 8.9–13.6) years. HIVTSQc outcomes favored DTG, with 88/92 (96%) HIVTSQc-Teen and 149/151 (99%) HIVTSQc-Parent responses indicating being “much more satisfied now” post-transition. Among 69 (28%) actigraphy participants, mean sleep period length was 9.0 hours (standard deviation [SD] 1.0) before and 9.2 hours (SD 1.0) 2–4 weeks post-transition (mean difference 0.2, 95% CI 0.0–0.4). Secondary outcomes did not change meaningfully. Conclusions: – Observed treatment satisfaction and tolerability support the rollout of DTG in pediatric HIV care.