Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study.

Ryom L, Mocroft A, Kirk O, Worm SW, Kamara DA, Reiss P, Ross M, Fux CA, Morlat P, Moranne O, Smith C, Lundgren JD.

J Infect Dis. 2013 May 1;207(9):1359-69. doi: 10.1093/infdis/jit043. Epub 2013 Feb 4.

BACKGROUND: Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown. METHODS: 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. RESULTS: Of 22 603 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. CONCLUSIONS: 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.

PMID: 23382571

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.