Background: Initiating newly diagnosed people living with human immunodeficiency virus (HIV) onto antiretroviral treatment (ART) and retaining patients on treatment are vital to South Africa’s ART programme. In 2020, coronavirus disease 2019 (COVID-19) and its accompanying containment (lockdown) measures presented unprecedented challenges to achieving these objectives.Aim: This study describes the impact of COVID-19 and related restrictions on district-level numbers of newly diagnosed people living with HIV and defaulting ART patients.Setting: Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape of South Africa.Methods: Mixed-methods approach: Monthly aggregated electronic patient data (newly initiated and restarted on ART) from 113 public healthcare (PHC) facilities were analysed (December 2019 to November 2020) across varying levels of COVID-19 lockdown regulation periods; telephonic in-depth interviews at 10 rural BCMM PHC facilities were conducted with facility staff, community health workers (CHWs) and intervention personnel.Results: The number of newly initiated ART patients decreased dramatically compared with pre-COVID-19 levels. The overall number of restarted ART patients increased in response to fears of co-infection with COVID-19. Facility-level communications and community outreach promoting HIV testing and treatment were disrupted. Novel approaches to providing services to ART patients were developed.Conclusion: Programmes for identifying undiagnosed people living with HIV and services aimed at retaining ART patients in care were profoundly impacted by COVID-19. The value of CHWs was highlighted, as were communication innovations.Contribution: This study describes the impact of COVID-19 and related regulations on HIV testing, ART initiation and adherence to treatment in a District of the Eastern Cape of South Africa.