Jens Lundgren1, Amanda Mocroft2, Lene Ryom1. 1. CHIP/PERSIMUNE, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK.
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.
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.
Authors: Derek Larson; Seung Hyun Won; Anuradha Ganesan; Ryan C Maves; Karl Kronmann; Jason F Okulicz; Xiuping Chu; Christina Schofield; Thomas O'Bryan; Brian K Agan; Robert Deiss Journal: HIV Med Date: 2021-10-26 Impact factor: 3.180
Authors: Gaetano Alfano; Gianni Cappelli; Francesco Fontana; Luca Di Lullo; Biagio Di Iorio; Antonio Bellasi; Giovanni Guaraldi Journal: J Clin Med Date: 2019-08-19 Impact factor: 4.241
Authors: Magda Opsomer; Dessislava Dimitrova; Johan Verspeelt; Amy Purrington; Abdul Mehbob; Scott Chavers; Helen Pai; Simon Vanveggel; Donghan Luo; Kimberley Brown; Christiane Moecklinghoff; Richard E Nettles; Katia Boven Journal: Drugs R D Date: 2018-09