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Background: Eswatini (formerly Swaziland) has one of the highest rates of TB and HIV co-disease in the world. Despite national efforts to improve service delivery and prevent TB and HIV transmission, rates remain high. A recent prospective, observational study of integrated, patient-selected IPT delivery showed extraordinary improvements in IPT adherence, running counter to previous assumptions. This prompted the need to understand contextual and unseen study factors that contributed to high rates of adherence., Objective: To investigate high rates of IPT adherence rates among people living with HIV who participated in an observational study comparing modes of IPT delivery., Methods: Community-based participatory research guided the development of in-person administration of semi-structured questionnaires. Observational and field note data were analyzed. Qualitative data were analyzed using content analysis., Results: We interviewed 150 participants and analyzed responses from the 136 who remembered being given a choice of their IPT delivery method. Fifty-seven percent were female and the median age was 42. Nearly 67% of participants chose to receive facility-based IPT. High rates of self-reported IPT treatment adherence were linked to four key concepts: 1) adherence was positively impacted by community education; 2) disclosure of status served to empower participant completion; 3) mode of delivery perceptions positively impacted adherence; and 4) choice of treatment delivery seen as helpful but not essential for treatment completion., Discussion: Achieving higher rates of IPT adherence in Eswatini and similar rural areas requires community-engaged education and outreach in coordination with care delivery systems., Competing Interests: This work was undertaken within the resources available to the authors via their institutions. The authors declare no financial or other conflicts of interest. Support for this work was provided by the TB CARE II project, which is funded by the United States Agency for International Development (USAID) under Cooperative Agreement Number AID-OAA-A-10-00021. The project’s prime recipient is the University Research Co, LLC (URC), Chevy Chase, MD, USA, and the Geisel School of Medicine at the Dartmouth Section of Infectious Disease and International Health, Hanover, NH, USA, is a sub-recipient. Any affiliation with home institutions does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors declare no financial or other conflicts of interest.