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

Jose, Sophie; Nelson, Mark; Phillips, Andrew; Chadwick, David; Trevelion, Roy; Jones, Rachael; Williams, Deborah I.; Hamzah, Lisa; Sabin, Caroline A.; Post, Frank A.; on behalf of the UK CHIC study

doi: 10.1097/QAD.0000000000001353
Clinical Science

Objective: 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.

Design: Cohort study.

Methods: 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 m2 per year) in all switchers and those with rapid eGFR decline (>5 ml/min per 1.73 m2 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.

Results: 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 m2. 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.

Conclusions: 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.

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

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. Tel: +0207 794 0500 ext. 36763; e-mail: sophie.jose@ucl.ac.uk

Received 16 August, 2016

Revised 31 October, 2016

Accepted 31 October, 2016

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