HIV INFECTIONS AND AIDS: Edited by David DockrellContemporary protease inhibitors and cardiovascular riskLundgren, Jensa; Mocroft, Amandab; Ryom, LeneaAuthor Information aCHIP/PERSIMUNE, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark bCentre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK Correspondence to Professor Amanda Mocroft, Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, Rowland Hill St, London NW3 2PF, UK. Tel: +44 207 7940500 ext 33194; e-mail: [email protected] Current Opinion in Infectious Diseases: February 2018 - Volume 31 - Issue 1 - p 8-13 doi: 10.1097/QCO.0000000000000425 Buy Metrics Abstract Purpose of review To review the evidence linking use of HIV protease inhibitors with excess risk of cardiovascular disease (CVD) in HIV+ populations. Recent findings For the two contemporary most frequently used protease inhibitors, darunavir and atazanavir [both pharmacologically boosted with ritonavir (/r)], darunavir/r has been shown to be associated with increased CVD risk. The effect is cumulative with longer exposure increasing risk and an effect size comparable to what has been observed for previously developed protease inhibitors. Biological mechanisms may be overlapping and include perturbed lipid metabolism and accumulation of cholesterol derivatives within macrophages. Conversely, atazanavir/r has not been shown to be associated with CVD, possibly because of its ability to increase cardioprotective bilirubin levels. Summary Evidence linking protease inhibitors to CVD is based on observational studies only, whereas plausible biological explanations are well established and derived from randomized trials and controlled experiments. Given the possible association with clinical disease, a conservative approach to apply the data in daily practise is proposed which is focused on individualization of care based on underlying risk of CVD. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.