Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors

Stein, James H.; Merwood, Michelle A; Bellehumeur, Jennifer L.; Aeschlimann, Susan E.; Korcarz, Claudia E.; Underbakke, Gail; Mays, Maureen E; Sosman, James M.

doi:10.1016/j.ahj.2003.10.018

Cited by 88 publications

(75 citation statements)

References 30 publications

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“…In addition, several HIV-infected subjects were on statin therapy, which may have a positive effect on brachial FMD and CIMT. Nevertheless, two recent studies of statin therapy in HIV found no more than a 0.7-1.2% improvement in brachial artery FMD with statin therapy [37,38], and the inclusion of statin-treated, HIV-infected subjects in the present study was felt to best reflect current standard of care for persons with HIV [39]. When further controlling for use of lipid-lowering medication, there were still no significant differences in FMD or CIMT between HIV-infected and control groups.…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

Mondy

Fuentes²,

Önen³

et al. 2008

Aids

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Objective-Cardiovascular disease risk among persons with HIV is likely multifactorial, thus testing a variety of available noninvasive vascular ultrasound and other surrogate tests may yield differing results. To address this issue, we assessed multiple metabolic and clinical predictors of endothelial function and carotid intima-media thickness in HIV-infected subjects and compared results with HIV-negative controls.Design-Prospective, cross-sectional study of 50 HIV-infected, healthy adults on stable highly active antiretroviral therapy matched to 50 HIV-negative controls by age, sex, race, and body mass index.Methods-Flow-mediated vasodilation of the brachial artery, carotid intima-media thickness, dual energy X-ray absorptiometry (HIV-infected subjects), and fasting insulin, lipids, and oral glucose tolerance tests were performed. Results were compared between HIV-infected and control groups.Results-Fifty percent of subjects were African-American with 34% women. Among HIVinfected, mean CD4 cell count was 547 cells/ µl; 90% had HIV RNA less than 50 copies/ml. There were no significant differences between HIV-infected and control subjects with regard to brachial artery flow-mediated vasodilation or carotid intima-media thickness. In multivariate analyses of the HIV cohort, independent predictors of endothelial dysfunction (lower flow-mediated vasodilation) were increasing insulin resistance, greater alcohol consumption, and higher baseline brachial artery diameter (P < 0.05); predictors of increased carotid intima-media thickness were hypertension, higher trunk/limb fat ratio, and insulin resistance (P < 0.05).Conclusion-In this HIV cohort on modern highly active antiretroviral therapy with well controlled HIV, there were no significant differences with regard to preclinical markers of cardiovascular disease. Insulin resistance was a strong predictor of impaired brachial artery flowmediated vasodilation and increased carotid intima-media thickness, and may be an important cardiovascular disease risk factor in the HIV population.

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Section: Discussionmentioning

confidence: 99%

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

Mondy

Fuentes²,

Önen³

et al. 2008

Aids

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“…Fibrates, however, were associated with a substantial increase of HDL-C and decrease of TG concentrations. Compared with other studies in HIVpositive individuals, the dyslipidaemia treatment applied here seems to be comparable in terms of lipid lowering [19,49].Fish oil supplementation was emphasized in the metabolic clinic. The results demonstrate that selective advice about natural health product use can help to reduce some of the risk factors for CVD in a subset of patients who remain on the treatment.…”

mentioning

confidence: 95%

“…Small clinical trials suggest that pravastatin and fluvastatin reduce concentrations of total and low-density lipoprotein cholesterol (LDL-C) without substantial adverse effects [18][19][20][21]. Pharmacokinetic studies suggest that simvastatin should be avoided and atorvastatin used with caution in persons taking ritonavir and saquinavir because of drug-drug interactions [22].…”

Section: Introductionmentioning

confidence: 99%

Use of metabolic drugs and fish oil in HIV‐positive patients with metabolic complications and associations with dyslipidaemia and treatment targets

et al. 2007

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BackgroundHighly active antiretroviral therapy (HAART) with protease inhibitors (PI) is successful in suppressing viral replication, but may lead to a range of metabolic abnormalities associated with cardiovascular disease (CVD). ObjectivesThe first objective of the study was to compare baseline demographic and clinical characteristics between PI users and non-PI users referred to a specialized metabolic clinic during [1999][2000][2001][2002][2003]. The second objective was to assess the associations of prescription drugs and fish oil with dyslipidaemia and to determine whether or not patients achieved treatment targets during 6 months of treatment. MethodsA retrospective analysis was performed using two sets of charts based on standardized forms with entries for personal data, drug treatment and clinical history. Anonymous linkage with the British Columbia HIV/AIDS Drug Treatment Program and the hospital laboratory was performed to gather information about HAART prescriptions and blood work. ResultsIn total, 237 patients were included in the study. There were few differences in any demographic or clinical factors between PI users and non-PI users. Compared with controls not taking lipid-lowering drugs or fish oil (n 5 48), statins appeared to be the only agent that was significantly associated with a reduced total cholesterol concentration ( À 15.6%; P 5 0.009). Fibrate treatment was associated with the largest reduction of triglyceride concentration ( À 37.4%; P 5 0.012), closely followed by fish oil (n 5 18; À 32%; P 5 0.027). Six-month treatment success rates ranged between 17 and 43% of patients for total cholesterol (o5.2 mmol/L) and between 15 and 44% of patients for triglycerides (o2.3 mmol/L). ConclusionsDespite the apparent lowering of blood lipids with drug and fish oil treatments, a majority of patients in these treatment groups (56.5-83.3%) still had elevated concentrations after 6 months. expectancy in HIV-positive men and women [2]. Although HAART regimens are able to suppress viral replication, there is evidence that some antiretroviral drugs are associated with a range of metabolic abnormalities that lead to cardiovascular disease (CVD) [3][4][5][6][7][8][9]. Numerous population-based cohort studies have suggested that some protease inhibitors (PIs) are more strongly associated with dyslipidaemia than others [10,11]. For example, hypertriglyceridaemia appears to be more frequent and more severe with ritonavir than with indinavir. In addition, the use of PIs has also been shown to more frequently result in endothelial dysfunction [12] and coronary artery calcification [13]. CVD may be caused by accelerated atherosclerosis [12,14] resulting from side effects of antiretroviral therapy (ART) such as dyslipidaemia, insulin resistance and lipodystrophy [15]. Compared with the general population of a similar age, HIV-positive patients have a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol (HDL-C) concentration, a higher prevalence of smoking, a higher mean waist-to-h...

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“…They found that endothelial function was impaired in HIV infected subjects on PI-containing regimen and HIV infected patients with no ARV use had a normal FMD and they concluded that protease inhibitors are associated with atherogenic lipoprotein changes and with endothelial dysfunction [98]. Two recent studies on the effect of statins on endothelial functions and lipid profile in HIV infected patients receiving protease inhibitors, showed that pravastatin reduced concentrations of atherogenic lipoproteins and that endothelial function tended to increase in patients receiving pravastatin; however, the difference between treatment regimen was not statically significant [98][99][100].…”

Section: Clinical Assessment Of Endothelium In Hiv Infectionmentioning

confidence: 99%

Endothelial function and cardiovascular diseases in HIV infected patient

Andrade¹,

Cotter²

2006

Braz J Infect Dis

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The HIV epidemic has dramatically changed the paradigm for the development of drug therapy in the last 15 years. The goal is now not only to provide an effective reduction of plasma viremia , but also to reconstitute the immune deficiency due to the progression of the disease. Significant problems with the metabolism of sugars and lipids lead to the appearance of well-documented disorders such as insulin resistance, abnormalities in lipid metabolism and lipodystrophy in those patients on prolonged therapy with antiretrovirals. The question of whether or not HAART-associated lipid disorders contribute to the premature development of coronary artery disease is of major importance for the HIV community. Endothelial injury is associated with disease-related biochemical abnormalities that are implicated in HIV pathogenesis. The exploration of endothelial function began in the early 1980s at the start of the epidemic. The study of endothelial function in HIV infection and its modifications by HAART is an exciting new field in clinical research; in this review the available information on cardiovascular diseases associated with HIV infection and its treatment are discussed.

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Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors

Cited by 88 publications

References 30 publications

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

Use of metabolic drugs and fish oil in HIV‐positive patients with metabolic complications and associations with dyslipidaemia and treatment targets

Endothelial function and cardiovascular diseases in HIV infected patient

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