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In March 2020, the South African government imposed a lockdown to control COVID-19 transmission. Lockdown may affect people living with HIV’s (PLWH) antiretroviral therapy (ART) adherence. Data from a cluster randomised control trial was collected from 152 PLWH in Cape Town sub-districts from October 2019–March 2020 when the lockdown halted collection. Subsequently, 83 PLWH were followed-up in June–July 2020. Random effects models were used to analyse: (1) changes between baseline and follow-up and (2) correlates of adherence during lockdown. At follow-up, there was an increase in the odds of being below the poverty line and the odds of experiencing violence decreased. Measures for well-being, household functioning, stigma and HIV competency improved. Violence, depression, food insecurity, and stigma were associated with poorer ART adherence; higher well-being scores were associated with better adherence. During lockdown, governments need to ensure financial support, access to (mental) health services, and services for those experiencing violence. Clinical Trial Number : Pan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019. Supplementary Information The online version contains supplementary material available at 10.1007/s10461-021-03541-0.

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