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Whilst several antiretroviral drugs have been associated with moderate chronic kidney disease (CKD), their contribution to advanced CKD and end-stage renal disease (ESRD) remain unknown.D:A:D participants with at least three estimated glomerular filtration rates (eGFR) after February 2004 were followed until the first of advanced CKD (confirmed eGFR ≤ 30 ml/min, ≥3 months apart), ESRD (dialysis ≥3 months/ transplantation), 6 months after last visit or February 2012.Poisson regression was used to assess risk factors for advanced CKD/ESRD including exposure to potential nephrotoxic antiretroviral drugs and antiretroviral drug discontinuation rates according to latest eGFR.Among 35 192 persons contributing 200 119 person years of follow-up (PYFU), 135 (0.4%) developed advanced CKD (n = 114)/ESRD (n = 21); incidence rate = 0.67 [95% confidence interval (CI), 0.56–0.79]/1000 PYFU. Tenofovir (TDF) was particularly frequently discontinued as eGFR declined. After adjustment, those previously exposed but currently off TDF had similar advanced CKD/ESRD rate ratios compared with those unexposed [1.00 (95% CI, 0.66–1.51)], while those currently on TDF had reduced rates [0.23 (95% CI, 0.13–0.41)]. No consistent associations with other antiretroviral drugs were seen. Results were robust after time-lagging antiretroviral drug exposure, stratifying by baseline eGFR, and allowing for competing risks. Other predictors were diabetes, hypertension, baseline eGFR, smoking and current CD4+ cell count. The incidence rate in nonsmokers with baseline eGFR > 60 and no diabetes or hypertension was 0.16 (95% CI 0.09–0.26)/1000 PYFU.Neither current nor recent antiretroviral drug use predicted advanced CKD/ESRD during 6 years median follow-up in a large, heterogenenous and primarily white cohort. TDF discontinuation rates increased with decreasing eGFR, leaving a selected group still on TDF at lower advanced CKD/ESRD risk. Traditional renal risk factors and current CD4+ cell count were the strongest advanced CKD/ESRD predictors.