Protease inhibitors and cardiovascular outcomes in patients with HIV-1

Division of HIV/AIDS Prevention, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
The Lancet (Impact Factor: 45.22). 12/2002; 360(9347):1747-8. DOI: 10.1016/S0140-6736(02)11672-2
Source: PubMed


Protease inhibitors for treatment of HIV-1 have been linked with increased risk of hyperlipidaemia and hyperglycaemia. In a cohort of 5672 outpatients with HIV-1 seen at nine US HIV clinics between January, 1993, and January, 2002, the frequency of myocardial infarctions increased after the introduction of protease inhibitors in 1996 (test for trend, p=0.0125). We noted that 19 of 3247 patients taking, but only two of 2425 who did not take, protease inhibitors had a myocardial infarction (odds ratio 7.1, 95% CI 1.6-44.3; Cox proportional hazards model-adjusted for smoking, sex, age, diabetes, hyperlipidaemia, and hypertension-hazard ratio 6.5, 0.9-47.8). Our findings suggest that, although infrequent, use of protease inhibitors is associated with increased risk of myocardial infarction in patients with HIV-1.

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    • "Several hypotheses have been formulated to explain a potential increase in the incidence of premature aging and coronary events in these patients [3, 4, 18–23]. Some mechanisms are related to antiretroviral therapy, such as the mitochondrial dysfunction and oxidative stress induced by thymidine analogues [10–12] or protease inhibitor- (PI-) related dyslipemia [8, 9, 13, 14], while the virus itself contributes to increased cardiovascular risk by a chronic inflammatory effect or a direct effect on endothelial and other cells [4, 20, 21]. These factors, together with the increased incidence of traditional CVRF in HIV-1-infected patients, could pave the way to the development of coronary events [4, 8–14, 16, 19–24]. "
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    ABSTRACT: Background: There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) in HIV-infected patients. Methods: We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. Results: We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus). Other CVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol (P = 0.025) and LDL-cholesterol (P = 0.004) was observed. However, the percentage of patients who maintained LDL-cholesterol > 100 mg/dL remained stable (from 46% to 41%, P = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time (P = 0.028). Conclusions: The prevalence of coronary events in our cohort is low. CVRF prevalence is high and their management is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.
    BioMed Research International 08/2014; 2014:823058. DOI:10.1155/2014/823058 · 3.17 Impact Factor
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    • "In other drugs in the same pharmacological group there were no similar observations (neither stavudine nor zidovudine). A significant rise of MI incidence among HIV-positive patients was observed after introduction of protease inhibitor (PI) on the market, and also treatment with PI was an independent risk factor of MI [30]. During therapy with PI development of lipodystrophy, hyperlipidemia, hyperglycemia and insulin resistance is possible even in 60% of patients. "
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    ABSTRACT: Myocardial infarction (MI) is most commonly caused by atherosclerosis and/or inflammatory processes of coronary artery walls. The consequence of those phenomena is instability of the atherosclerotic plaque, activation of the coagulation cascade and thrombus formation which occludes the lumen of the vessel. Vasospasm and microembolisation may participate in MI pathogenesis. In young individuals with diagnosis of MI, coronarography often reveals no pathologies. Is reported that MIs without significant changes of the coronary arteries occur in 1% to 12% of patients. In this article we focus on chemical substances, medicines among them, which can be a cause of MI.
    Postepy w Kardiologii Interwencyjnej / Advances in Interventional Cardiology 09/2013; 9(3):250-5. DOI:10.5114/pwki.2013.37504 · 0.15 Impact Factor
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    • "The development and widespread use of highly active antiretroviral therapy (HAART) has drastically increased the life expectancy of HIV patients; however, HAART drugs have been implicated in the early on-set and increased risk of numerous co-morbidities, including cancers, central nervous system disorders , pulmonary disease, renal disease, hepatic disease, diabetes, and cardiovascular disease. Cardiovascular complications include increased incidence of myocardial infarction (Friis-Møller et al., 2003; Mary-Krause et al., 2003; Holmberg et al., 2002) and atherosclerotic lesions (Maggi et al., 2004; Spieker et al., 2005) and elevated preclinical markers of atherosclerosis (e.g., increased carotid intima-media thickness (c-IMT) (van Vonderen et al., 2009; Hsue et al., 2004; Ross et al., 2008), arterial stiffening (van Vonderen et al., 2009; Bonnet et al., 2004; Sevastianova et al., 2005), and impaired flow mediated dilation (FMD) (Bonnet et al., 2004; Calmy et al., 2009; Shankar et al., 2005). Antiretrovirals are typically prescribed in cocktails of three drugs; thus, the roles of specific HAART drugs in the development of atherosclerosis are difficult to determine from clinical data (Lundgren et al., 2008; Worm et al., 2010); viral infection may also play a significant role, further complicating the interpretation of clinical data (Oliviero et al., 2009; Hsue et al., 2009; El-Sadr et al., 2006). "
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    ABSTRACT: HIV positive patients on highly active antiretroviral therapy (HAART) have shown elevated incidence of a number of non-AIDS defining co-morbidities, including cardiovascular disease. Given that HAART regimens contain a combination of at least three drugs, that disease management often requires adjustment of these regimens, and HIV, independent of HAART, also plays a role in development of co-morbidities, determining the role of specific HAART drugs and HIV infection itself from clinical data remains challenging. To characterize specific mediators and underlying mechanisms of disease, in vitro and in vivo animal models are required, in parallel with clinical data. Given its low cost azidothymidine (AZT) contributes to the backbone of a large proportion of HAART treated patients in the developing world where much of the global burden of HIV resides. The goal of this study was to test the hypothesis that AZT can lead to proatherogenic changes including the subclinical markers of arterial stiffening and intima-media thickening in mice. AZT (100mg/kg) or vehicle was administered to wild-type FVB/N mice via oral gavage for 35 days. Cylindrical biaxial biomechanical tests on the common carotid arteries and suprarenal aortas exhibited arterial stiffening in AZT mice compared to controls. Multiphoton microscopy and histology demonstrated that AZT led to increased intima-media thickness. These data correlated with decreased elastin content and increased protease activity as measured by cathepsin zymography; no differences were observed in collagen content or organization, in vivo axial stretch, or opening angle. Thus, this study suggests the drug AZT has significant effects on the development of subclinical markers of atherosclerosis.
    Journal of Biomechanics 04/2013; 46(9). DOI:10.1016/j.jbiomech.2013.03.021 · 2.75 Impact Factor
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