Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir.

Sophie Jose,Lisa Hamzah,Mark Nelson,Rachael Jones,Caroline A Sabin,David Chadwick,Andrew Phillips,Roy Trevelion,Deborah I Williams,Frank A Post

doi:10.1097/qad.0000000000001353

Abstract

Atazanavir (ATV) and lopinavir (LPV) have been associated with kidney disease progression in HIV positive patients, with no data reported for darunavir (DRV). We examined kidney function in patients who switched their protease inhibitor from ATV or LPV to DRV. Cohort study. Data were from the UK CHIC study. We compared pre and post switch estimated glomerular filtration rate (eGFR) slopes (expressed in ml/min per 1.73 m per year) in all switchers and those with rapid eGFR decline (>5 ml/min per 1.73 m per year) on ATV or LPV. Mixed-effects models were adjusted for age, gender, ethnicity, eGFR at switch and time updated CD4 cell count, HIV RNA and cumulative tenofovir (tenofovir disoproxil fumarate) exposure. Data from 1430 patients were included. At the time of switching to DRV, median age was 45 years, 79% were men, 76% had an undetectable viral load, and median eGFR was 93 ml/min per 1.73 m. Adjusted mean (95% confidence interval) pre and post switch eGFR slopes were -0.84 (-1.31, -0.36) and 1.23 (0.80, 1.66) for ATV (P < 0.001), and -0.57 (-1.09, -0.05) and 0.62 (0.28, 0.96) for LPV (P < 0.001). Stable or improved renal function was observed in patients with rapid eGFR decline on ATV or LPV who switched to DRV [-15.27 (-19.35, -11.19) and 3.72 (1.78, 5.66), P < 0.001 for ATV, -11.93 (-14.60, -9.26) and 0.87 (-0.54, 2.27), P < 0.001 for LPV]. Similar results were obtained if participants who discontinued tenofovir disoproxil fumarate at the time of switch were excluded. We report improved kidney function in patients who switched from ATV or LPV to DRV, suggesting that DRV may have a more favourable renal safety profile.

Highlights

Antiretroviral therapy (ART) allows people living with HIV to achieve a normal life expectancy [1]
The improvements in estimated glomerular filtration rate (eGFR) slope were observed in patients who received ATV or LPV with tenofovir disoproxil fumarate (TDF) and much more pronounced in study participants who had experienced rapid eGFR decline or renal impairment prior to protease inhibitor switch
Our data suggest that ATV and LPV, especially when coadministered with TDF, may result in kidney injury and that switching these protease inhibitor to DRV may preserve renal function

Summary

Introduction

Antiretroviral therapy (ART) allows people living with HIV to achieve a normal life expectancy [1]. Widespread use of ART has resulted in ageing HIV populations in whom comorbidities such as chronic kidney disease (CKD), hypertension, diabetes, and cardiovascular disease are increasingly prevalent, diagnosed earlier than in the general aResearch Department of Infection and Population Health, University College London, bChelsea and Westminster NHS Foundation Trust, London, cSouth Tees Hospitals NHS Foundation Trust, Middlesbrough, dHIV I-Base, London, eBrighton and Sussex University Hospitals, Brighton, and fKings College Hospital NHS Foundation Trust, London, UK. Correspondence to Sophie Jose, Research Department of Infection and Population Health, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.

Methods

Results

Conclusion