Exposure to Antiretrovirals and Risk of Chronic Kidney Disease in HIV-positive Patients with Normal Renal Function: A Single Center Cohort Study

Some antiretrovirals, including tenofovir disoproxil fumarate (TDF), have been associated with increased risk of chronic kidney disease (CKD). We performed a retrospective cohort study of adult HIV-positive patients seen at the University of Kansas medical center, with initial estimated glomerular filtration rate (eGFR) > 90 ml/minute/1.73 m2. Patients were followed from initial eGFR measurement until one of the following: CKD, last eGFR measurement plus 3 months or Nov 29, 2016 (whichever occurred first). CKD was defined as sustained eGFR < 60 ml/minute/1.73 m2for at least 3 months. Poisson regression was used to estimate the incidence rate of CKD associated with exposure to TDF, ritonavir-boosted atazanavir (ATV/r), ritonavir boosted lopinavir (LPV/r), or nucleoside reverse transcriptase inhibitors (NRTIs) excluding TDF. Between January 1, 2004 and November 29, 2016, 518 eligible patients were included. Participants had a median age 37.5 years, a median CD4 count of 488 cells/uL and a median baseline eGFR of 111 ml/minute/1.73m2. During 1963.5 person-years of follow-up (at a median of 3.1 years; IQR 1.94-8.24), 10 (1.9%) of 518 patients developed CKD (incidence 5.09 per 1,000 person-years of follow-up; 95% CI 1.94-8.24). On univariate analysis age, body mass index (BMI) < 26 kg/m2, anemia, and nadir CD4 < 200 were associated with increased CKD. On multivariate analysis, variables associated with increased risk of CKD were time on TDF (adjusted Incidence Rate Ratio (aIRR) 1.236 per year of exposure; 95% CI 1.0284–1.409; P = 0.002), current NRTI excluding TDF use (aIRR 10.692; 95% CI 2.184–52.352; P = 0.003), and prior NRTI use excluding TDF (aIRR 10.686; 95% CI 1.730–65.983; P = 0.011). BMI > 26 kg/m2 was associated with decreased risk of CKD (aIRR 0.053; 95% CI 0.004–0.629; P = 0.020). Time on NRTIs excluding TDF was not associated with increased CKD risk. The incidence of CKD in this cohort of HIV-positive patients with normal renal function is higher than reported in the literature. Time on TDF was associated with increased risk of CKD as previously reported. Tenofovir alafenamide (TAF) is available and associated with less nephrotoxicity, most patients are being switched from TDF to TAF. The increased risk of CKD with exposure to NRTIs excluding TDF could be due to residual confounding. All authors: No reported disclosures.