Cardiovascular risks associated with protease inhibitors for the treatment of HIV

Expert Opin Drug Saf. 2021 Nov;20(11):1351-1366. doi: 10.1080/14740338.2021.1935863. Epub 2021 Jul 26.


Introduction: Cumulative use of some first-generation protease inhibitors has been associated with higher rates of dyslipidemia and increased risk of cardiovascular disease. The protease inhibitors most commonly in use are atazanavir and darunavir, which have fewer detrimental lipid effects and greater tolerability. This paper aims to review the evidence of a potential association of these contemporary protease inhibitors with the risk of ischemic CVD and atherosclerotic markers.Areas covered: We searched for publications of randomized trials and observational studies on PubMed from 1 January 2000 onwards, using search terms including: protease inhibitors; darunavir; atazanavir; cardiovascular disease; cardiovascular events; dyslipidemia; mortality; carotid intima media thickness; arterial elasticity; arterial stiffness and drug discontinuation. Ongoing studies registered on as well as conference abstracts from major HIV conferences from 2015-2020 were also searched.Expert opinion: Atazanavir and darunavir are no longer part of first-line HIV treatment, but continue to be recommended as alternative first line, second- and third-line regimens, as part of two drug regimens, and darunavir is used as salvage therapy. Although these drugs will likely remain in use globally for several years to come, baseline CVD risk should be considered when considering their use, especially as the population with HIV ages.

Keywords: Atazanavir; atherosclerotic markers; boosters; cardiovascular disease; clinical management; darunavir; hiv.

Publication types

  • Review

MeSH terms

  • Animals
  • Atazanavir Sulfate / administration & dosage
  • Atazanavir Sulfate / adverse effects
  • Atherosclerosis / etiology
  • Cardiovascular Diseases / etiology*
  • Darunavir / administration & dosage
  • Darunavir / adverse effects
  • Dyslipidemias / chemically induced
  • Dyslipidemias / complications
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / adverse effects*
  • Heart Disease Risk Factors
  • Humans
  • Randomized Controlled Trials as Topic


  • HIV Protease Inhibitors
  • Atazanavir Sulfate
  • Darunavir