CHIP/PERSIMUNE, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK.
Curr Opin Infect Dis. 2018 Feb;31(1):8-13. doi: 10.1097/QCO.0000000000000425.
To review the evidence linking use of HIV protease inhibitors with excess risk of cardiovascular disease (CVD) in HIV+ populations.
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.
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.
HIV 阳性人群中使用 HIV 蛋白酶抑制剂与心血管疾病（CVD）风险增加之间关联的证据。
对于目前使用最广泛的两种蛋白酶抑制剂，达芦那韦和阿扎那韦[两者均与利托那韦（/r）联合药理学增强]，达芦那韦/r 已被证明与 CVD 风险增加相关。这种影响是累积的，暴露时间越长，风险越高，与之前开发的蛋白酶抑制剂观察到的效果相当。生物学机制可能重叠，包括脂质代谢紊乱和胆固醇衍生物在巨噬细胞内的积累。相反，阿扎那韦/r 与 CVD 无关，可能是因为它能够增加保护性胆红素水平。
将蛋白酶抑制剂与 CVD 联系起来的证据仅基于观察性研究，而合理的生物学解释则是基于随机试验和对照实验确立的。鉴于与临床疾病可能存在关联，建议在日常实践中谨慎应用这些数据，根据 CVD 的潜在风险，个体化治疗。
