Protease inhibitor exposure and increased risk of cardiovascular disease in HIV‐infected patients

Abstract

ObjectivesTo study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV-infected patients. MethodsWe estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIVinfected patients using a time-dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted. ResultsOf a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person-years of follow-up (PYFU) in the PI-exposed and nonexposed groups, respectively (P 5 0.0008). PI exposure 60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HR adj ) 1.71; 95% confidence interval (CI) 1.08-2.74; P 5 0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HR adj 1.90; 95% CI 1.13-3.20; P 5 0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre-existing CVD. ConclusionsPatients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV-infected patients.Keywords: antiretroviral therapy, cardiovascular disease, HAART, protease inhibitors, treatment complications IntroductionHighly active antiretroviral therapy (HAART) has resulted in dramatic declines in progression to AIDS and AIDS mortality in HIV-infected persons [1][2][3][4][5][6]. In some reports, death from nonAIDS-related causes exceed those attributed to AIDS in this patient population [2,[7][8][9], and cardiovascular deaths are increasing in these patients [1,2]. Recent reports suggest a shift in the relative cause of death among HIV-infected individuals, with cardiovascular deaths accounting for fewer than 4% of all deaths pre-1997 [1,10], and for 7-10% in more recent years [8,10,11].Reports from large observational studies demonstrate that considerable controversy exists over the association of HAART, particularly protease inhibitor (PI) therapies, with increased cardiovascular disease (CVD) risk [12][13][14][15][16][17]. PIs have been associated with alterations in surrogate markers of CVD, including coronary calcium scores and endothelial function [18,19], as well as with metabolic complications such as hyperlipidaemia, fat redistribution, insulin resistance, hypertension and diabetes mellitus [19][20][21][22][23][24]. Also, HIV-infected patients may have a higher prevalence of traditional CVD risk factors such as smoking than the general population [20,21]. In addition, as the mean age of the HIV-infected patient population has increased as a result of longer life expectancy with the disease, the consequent cardiovascular risk has also increased. 37These changes in patient demographics and the increasing prevalence of traditional CVD risk factors such as smoking, along with the increasing prevalence of PIassociated metabolic complications, have clearly increased the risk of CVD in HIV-infected individuals. ...

Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy

“…1,2 Although the initial focus was primarily on the relationship between dyslipidemia associated with antiretroviral therapy (ART) and cardiovascular risk, a broader appreciation of the complex interplay between traditional risk factors for CVD and HIV infection has emerged more recently. Several groups of investigators have designed studies to examine various aspects of the relationship between HIV infection, traditional cardiovascular risk factors, ART, and short-and longer-term cardiovascular risk [3][4][5][6][7][8][9][10][11] (see also Working Group 1). Studies have included both clinical end points (MI, hospitalization for MI or angina, and revascularization) and surrogate markers of atherosclerosis (endothelial function or carotid intima-media thickness).…”

HIV infection, aging and cardiovascular disease: epidemiology and prevention

“…4,22,[25][26][27][28][29][30][31] Compared with non-smokers, smokers have a two-fold or greater increased risk of MI 19 and CVD. 24,32 Although two studies have reported decreasing rates of smoking over time, in part suggesting that in an aging cohort, smoking rates are decreasing, 4,5 few data are available on actual rates of smoking as HIV-positive patients age. In the Swiss HIV Cohort Study, the prevalence of current smoking was lower among men older than 40 years compared with younger men (52.5% v. 64.3%, respectively), but not in women (53.4% v. 53.9%).…”

“…11 The contribution of smoking on the risk of CVD is significant and, in some cases, greater than many other CVD risk factors. 19,24 Current smoking has been reported in 40% to 70% of HIV-positive patients, two-to three-fold greater than the general population. 4,22,[25][26][27][28][29][30][31] Compared with non-smokers, smokers have a two-fold or greater increased risk of MI 19 and CVD.…”

Predicting the risk of cardiovascular disease in HIV-infected patients: the Data collection on Adverse Effects of Anti-HIV Drugs Study

“…Evidence from the Data collection on Adverse Effects of Anti-HIV Drugs Study(DAD) and other studies has established that exposure to certain antiretroviral drugs is associated with an increase in the rate of cardiovascular disease (CVD) events [1][2][3][4][5][6][7]. Of particular use in individual patient management would be a risk equation that could be used to identify HIV-positive patients at high risk of CVD events.…”