ABSTRACTAnti-retroviral treatment (ART) has improved the survival of people living with HIV in Africa. Living with chronic HIV comes with new health and functional challenges and the need to manage ART adherence. The Sepo Study applied disability frameworks to better understand living with chronic HIV while using ART. The study followed 35 people (18 women, 17 men) living with HIV and on ART 6 months or longer in private and public health facilities in Lusaka, Zambia over 18-months (2012–2015). A total of 99 in-depth interviews were conducted. Conventional content analysis and NVIVOv10 were applied to analyse the data. Participants were adhering to ART at the times of the interviews and therefore less likely to report major challenges with adherence. Three main themes emerged from the data related to adherence. Firstly, ART was regarded as “giving life”, which underscored adherence. Secondly, all participants described strategies for to managehealth and functional limitations, which they attributed as side-effects or chronicity. Thirdly, participants described experiences of uncertainty, including the efficacy of new regimens, potential loss of functioning, risk of new health problems, and death. Long-term ART managment in Africa needs to integrate rehabilitation approaches to address functional limitations, uncertainties, strengthen and support for adherence.