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Long-term virologic responses to antiretroviral therapy among HIV-positive patients entering adherence clubs in Khayelitsha, Cape Town, South Africa: a longitudinal analysisIntroduction In South Africa, an estimated 4.6 million people were accessing antiretroviral therapy (ART) in 2018. As universal Test and Treat is implemented, these numbers will continue to increase. Given the need for lifelong care for millions of individuals, differentiated service delivery models for ART services such as adherence clubs (ACs) for stable patients are required. In this study, we describe long‐term virologic outcomes of patients who have ever entered ACs in Khayelitsha, Cape Town. Methods We included adult patients enrolled in ACs in Khayelitsha between January 2011 and December 2016 with a recorded viral load (VL) before enrolment. Risk factors for an elevated VL (VL >1000 copies/mL) and confirmed virologic failure (two consecutive VLs >1000 copies/mL one year apart) were estimated using Cox proportional hazards models. VL completeness over time was assessed. Results Overall, 8058 patients were included in the analysis, contributing 16,047 person‐years of follow‐up from AC entry (median follow‐up time 1.7 years, interquartile range [IQR]:0.9 to 2.9). At AC entry, 74% were female, 46% were aged between 35 and 44 years, and the median duration on ART was 4.8 years (IQR: 3.0 to 7.2). Among patients virologically suppressed at AC entry (n = 8058), 7136 (89%) had a subsequent VL test, of which 441 (6%) experienced an elevated VL (median time from AC entry 363 days, IQR: 170 to 728). Older age (adjusted hazard ratio [aHR] 0.64, 95% confidence interval [CI] 0.46 to 0.88), more recent year of AC entry (aHR 0.76, 95% CI 0.68 to 0.84) and higher CD4 count (aHR 0.67, 95% CI 0.54 to 0.84) were protective against experiencing an elevated VL. Among patients with an elevated VL, 52% (150/291) with a repeat VL test subsequently experienced confirmed virologic failure in a median time of 112 days (IQR: 56 to 168). Frequency of VL testing was constant over time (82 to 85%), with over 90% of patients remaining virologically suppressed. Conclusions This study demonstrates low prevalence of elevated VLs and confirmed virologic failure among patients who entered ACs. Although ACs were expanded rapidly, most patients were well monitored and remained stable, supporting the continued rollout of this model.