Abstract Body

Prior studies have linked exposure to protease inhibitors (PIs) with excess risk of chronic kidney disease (CKD). Whether such safety signals remain for more contemporary PIs, such as darunavir (DRV/r), remains unclear.

D:A:D participants with >3 estimated glomerular filtration rate (eGFR) measurements, were followed from their first eGFR>60 mL/min/1.73m[sup]2[/sup] after 1.1.2009 to the earliest of CKD (confirmed, >3 months apart, eGFR<60 mL/min/1.73m[sup]2[/sup]), last visit plus 6 months or 1.2.2015. Poisson regression was used to model associations between CKD and use of two contemporary PI’s (ritonavir boosted atazanavir (ATV/r) and DRV/r), adjusting for demographics, other antiretroviral treatment, renal and HIV-related risk factors.

Of 26,939 persons 1,209 developed CKD (incidence rate (IR) 8.6/1000 PYFU [95%CI 8.1-9.1]). 13.1% and 24.8% of the follow-up time (140,966 PYFU) was after starting DRV/r and ATV/r respectively. Median age at baseline was 44 (IQR 38-50) years, median CD4 count was 510 (IQR 370-700) cells/mm3, and 28.8%, 35.9% and 35.3% were at low, medium and high 5-year CKD risk estimated by the D:A:D CKD risk score. While the CKD IR was low in individuals unexposed to DRV/r or ATV/r and increased with increasing exposure, after adjustment, only ATV/r (adjusted IR ratio (aIRR) 1.86 [1.58-2.20]), but not DRV/r (1.29 [0.94-1.77]) exposure remained significantly associated with CKD after >4 years (figure). Further multivariate analysis excluding those unexposed to DRV/r showed no statistically significant association between increasing DRV/r exposure and CKD (aIRR 1.21/5 years [0.83-1.75]). After exclusion of those unexposed to ATV/r the CKD rate significantly increased with increasing ATV/r exposure (aIRR 1.24/5 years [1.01-1.52]). The results were similar for individuals at low, medium or high estimated CKD risk (p>0.05, test for interaction). The rate of discontinuing ATV/r, but not DRV/r, was associated with lower eGFR levels (aIRR 1.74 [1.36–2.22] for ATV/r and 1.24 [0.83-1.86] for DRV/r at eGFR<70 vs. >90).

In a large heterogeneous cohort of contemporarily treated HIV-positive persons with six years median follow-up, DRV/r discontinuation was eGFR unrelated and more extended DRV/r use was not significantly associated with excess CKD risk, although a similar association as seen with ATV/r could not be ruled out. The previously reported association between gradually increasing risks of CKD with longer use of ATV/r remained.