BACKGROUNDThe World Health Organization recommends dolutegravir (DTG) as the backbone for first-line and second-line antiretroviral therapy (ART) worldwide. However, little is known about the acceptability and tolerability of DTG-based ART at routine points-of-care in Uganda. We set out to explore the perceptions of ART clinic managers regarding the acceptability and tolerability of DTG-based ART since national roll-out in March 2018 in Uganda.METHODSWe adopted a qualitative descriptive design involving 49 ART clinic managers and clinicians. Between September 2020 and February 2021, we conducted 22 in-depth interviews with ART clinic managers and clinicians in 12 purposively selected health facilities across Uganda. The selection of study sites ensured diversity in facility ownership-type (public/private), level of service delivery (tertiary/secondary/primary) and the four major geographic sub-regions of Uganda. We conducted three focus group discussions with 27 ART clinicians in the participating facilities. Data were analyzed by thematic approach. RESULTSThe participants acknowledged that DTG-based ART is well tolerated by the majority of their patients who appreciate the reduced pill burden, perceived less side effects and superior viral load suppression. However, they reported that a number of patients experience adverse drug reactions (ADRs) after being transitioned to DTG. Hyperglycemia is, by far, the most commonly reported suspected ADR associated with DTG-based regimens and was cited in all but two participating facilities. Insomnia, weight gain and reduced libido are among the other frequently cited suspected ADRs. In addition, ART clinic managers perceived some of the suspected ADRs as resulting from drug interactions between dolutegravir and isoniazid. Weak diagnostic capacities and shortage of associated commodities (e.g. glucometers and test kits) were reported as impediments to understanding the full extent of ADRs associated DTG-based ART. CONCLUSIONWhile DTG-based regimens were perceived to be well tolerated by the majority of patients at participating facilities, a number of patients were reported to experience suspected ADRs key among which were hyperglycemia, insomnia and reduced libido. We recommend interventions aimed at strengthening blood glucose monitoring for patients taking DTG-based regimens and precautionary assessment of all patients prior to initiating them on DTG for known risk factors for DTG related ADRs.