Ryom, L et al. Use of Contemporary Protease Inhibitors and Risk of Incident Chronic Kidney Disease in Persons with HIV: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. J Infect Dis 2019; 220:1629-34.

Data from HIV observational cohorts including D:A:D have found an association between the incidence of chronic kidney disease (CKD) and cumulative exposure to protease inhibitors (PIs) including indinavir, ritonavir-boosted lopinavir, and ritonavir-boosted atazanavir (ATV/r). Suggested mechanisms of renal insult include crystalluria, urolithiasis, and interstitial nephritis. The link of CKD with ritonavir-boosted darunavir (DRV/r) has generally been limited to case reports. This paper from the D:A:D cohort which includes patients from the U.S., Europe, and Australia looked at the association of CKD (eGFR <60 mL/min) and the use of ATV/r and DRV/r in patients followed from 2009 to 2016. The authors adjusted for age, sex, presence of renal risk factors (diabetes, HTN), CD4 count, hepatitis co-infection and other antiretrovirals that can affect renal function including tenofovir disoproxil fumarate. After excluding persons with CKD at baseline, there were 27,675 patients included in the analysis. The median baseline age was 44 years and 74% were male. Kidney disease developed in 1642 persons (6%) during a median follow-up of almost 7 years. After adjusting for confounding factors, cumulative exposure to ATV/r but not DRV/r remained significantly associated with an increased risk of CKD.

Author’s Commentary:

This study provides some good safety data regarding the long-term use of DRV/ritonavir – and likely DRV/cobicistat, although this latter combination was not specifically addressed in this study. The use of ATV has significantly declined in recent years which is good, as in this D:A:D cohort ATV was associated with a 40% increase in CKD incidence after 4 years of use. Collectively, fewer patients are taking PIs although most patients with multi-class resistance still have a PI as part of their ART regimen and would be expected to stay on these agents long-term until newer salvage agents are available.