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Association Between Antiretroviral Exposure and Renal Impairment Among HIV-Positive Persons With Normal Baseline Renal Function: the D:A:D Study(a)

D:A:D study participants with an estimated glomerular filtration rate (eGFR) of >= 90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of < 70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or < 60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD]) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements >= 3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression. Of 22603 persons, 468 (2.1%) experienced a confirmed eGFR of < 70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval {; ; ; ; ; CI}; ; ; ; ; , 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of >= 90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1.12-1.25]) and ritonavir-boosted atazanavir use (aIRR, 1.19/year [95% CI, 1.09-1.32]) were independent predictors of a confirmed eGFR of < 70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year [95% CI, 1.05-1.17] and 1.22/year [95% CI, 1.16- 1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs. Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

Anti-Retroviral Agents/ administration & dosage/ adverse effects; cohort studies; Glomerular Filtration Rate; HIV Infections/ drug therapy

Corporate Authors: D:A:D Study Group.