Background South Africa has undergone multiple expansions in antiretroviral therapy (ART) eligibility from an initial CD4+ threshold of ≤200 cells/μl to providing ART for all people living with HIV (PLWH) as of September 2016. We evaluated the association of programmatic changes in ART eligibility with loss from care, both prior to ART initiation and within the first 16 weeks of starting treatment, during a period of programmatic expansion to ART treatment at CD4+ ≤ 350 cells/μl. Methods and findings We performed a retrospective cohort study of 4,025 treatment-eligible, non-pregnant PLWH accessing care in a community health center in Gugulethu Township affiliated with the Desmond Tutu HIV Centre in Cape Town. The median age of participants was 34 years (IQR 28–41 years), almost 62% were female, and the median CD4+ count was 173 cells/μl (IQR 92–254 cells/μl). Participants were stratified into 2 cohorts: an early cohort, enrolled into care at the health center from 1 January 2009 to 31 August 2011, when guidelines mandated that ART initiation required CD4+ ≤ 200 cells/μl, pregnancy, advanced clinical symptoms (World Health Organization [WHO] stage 4), or comorbidity (active tuberculosis); and a later cohort, enrolled into care from 1 September 2011 to 31 December 2013, when the treatment threshold had been expanded to CD4+ ≤ 350 cells/μl. Demographic and clinical factors were compared before and after the policy change using chi-squared tests to identify potentially confounding covariates, and logistic regression models were used to estimate the risk of pre-treatment (pre-ART) loss from care and early loss within the first 16 weeks on treatment, adjusting for age, baseline CD4+, and WHO stage. Compared with participants in the later cohort, participants in the earlier cohort had significantly more advanced disease: median CD4+ 146 cells/μl versus 214 cells/μl (p < 0.001), 61.1% WHO stage 3/4 disease versus 42.8% (p < 0.001), and pre-ART mortality of 34.2% versus 16.7% (p < 0.001). In total, 385 ART-eligible PLWH (9.6%) failed to initiate ART, of whom 25.7% died before ever starting treatment. Of the 3,640 people who started treatment, 58 (1.6%) died within the first 16 weeks in care, and an additional 644 (17.7%) were lost from care within 16 weeks of starting ART. PLWH who did start treatment in the later cohort were significantly more likely to discontinue care in, In a retrospective cohort study, Ingrid Katz and colleagues report on the continuity of care for people with HIV in Gugulethu Township, South Africa, Author summary Why was this study done? Global HIV treatment initiatives have focused on increasing access to antiretroviral therapy, with the goal of creating an “AIDS-free generation.” In line with guidelines put forth by the World Health Organization, the focus is on starting newly diagnosed people on immediate treatment and maintaining long-term retention in care. There is growing evidence, however, that treatment availability alone is insufficient to stop the spread of the disease. In countries where HIV is hyperendemic such as South Africa, it remains unclear if expanding treatment eligibility to all individuals living with HIV will have an impact on patients’ engagement in care and early retention on treatment. We performed this study in a large, urban community HIV treatment site in Cape Town to understand the association of South Africa’s expanding treatment program with pre-treatment loss from care and early loss from care during treatment. What did the researchers do and find? We performed a retrospective study of 2 cohorts (which included over 4,000 treatment-eligible people living with HIV in total) who entered care at a community health center in Cape Town: an early cohort, enrolled into care from January 2009 to August 2011, when guidelines mandated that ART initiation required a CD4+ cell count of ≤200 cells/μl, pregnancy, advanced clinical symptoms (World Health Organization stage 4), or comorbidity (active tuberculosis), and a later cohort, enrolled September 2011 to December 2013, when the treatment threshold had been expanded to CD4+ ≤ 350 cells/μl. We determined the risk of pre-treatment and early losses (