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      Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study

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          Abstract

          Objectives: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. Methods: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. Results: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively ( p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C ( p = 0.45) and triglycerides ( p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction- p value = 0.002). Conclusions: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.

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          Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.

          Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.
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            Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease.

            Metabolic changes and smoking are common among HIV patients and may confer increased cardiovascular risk. The aim of the study was to determine acute myocardial infarction (AMI) rates and cardiovascular risk factors in HIV compared with non-HIV patients in two tertiary care hospitals. We conducted a health care system-based cohort study using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients. AMI rates were determined among patients receiving longitudinal care between October 1, 1996, and June 30, 2004. The primary outcome was myocardial infarction, identified by International Classification of Diseases coding criteria. AMI was identified in 189 HIV and 26,142 non-HIV patients. AMI rates per 1000 person-years were increased in HIV vs. non-HIV patients [11.13 (95% confidence interval [CI] 9.58-12.68) vs. 6.98 (95% CI 6.89-7.06)]. The HIV cohort had significantly higher proportions of hypertension (21.2 vs. 15.9%), diabetes (11.5 vs. 6.6%), and dyslipidemia (23.3 vs. 17.6%) than the non-HIV cohort (P < 0.0001 for each comparison). The difference in AMI rates between HIV and non-HIV patients was significant, with a relative risk (RR) of 1.75 (95% CI 1.51-2.02; P < 0.0001), adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. In gender-stratified models, the unadjusted AMI rates per 1000 person-years were higher for HIV patients among women (12.71 vs. 4.88 for HIV compared with non-HIV women), but not among men (10.48 vs. 11.44 for HIV compared with non-HIV men). The RRs (for HIV vs. non-HIV) were 2.98 (95% CI 2.33-3.75; P < 0.0001) for women and 1.40 (95% CI 1.16-1.67; P = 0.0003) for men, adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. A limitation of this database is that it contains incomplete data on smoking. Smoking could not be included in the overall regression model, and some of the increased risk may be accounted for by differences in smoking rates. AMI rates and cardiovascular risk factors were increased in HIV compared with non-HIV patients, particularly among women. Cardiac risk modification strategies are important for the long-term care of HIV patients.
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              Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT).

              The 356,222 men aged 35 to 57 years, who were free of a history of hospitalization for myocardial infarction, screened by the Multiple Risk Factor Intervention Trial (MRFIT) in its recruitment effort, constitute the largest cohort with standardized serum cholesterol measurements and long-term mortality follow-up. For each five-year age group, the relationship between serum cholesterol and coronary heart disease (CHD) death rate was continuous, graded, and strong. For the entire group aged 35 to 57 years at entry, the age-adjusted risks of CHD death in cholesterol quintiles 2 through 5 (182 to 202, 203 to 220, 221 to 244, and greater than or equal to 245 mg/dL [4.71 to 5.22, 5.25 to 5.69, 5.72 to 6.31, and greater than or equal to 6.34 mmol/L]) relative to the lowest quintile were 1.29, 1.73, 2.21, and 3.42. Of all CHD deaths, 46% were estimated to be excess deaths attributable to serum cholesterol levels 180 mg/dL or greater (greater than or equal to 4.65 mmol/L), with almost half the excess deaths in serum cholesterol quintiles 2 through 4. The pattern of a continuous, graded, strong relationship between serum cholesterol and six-year age-adjusted CHD death rate prevailed for nonhypertensive nonsmokers, nonhypertensive smokers, hypertensive nonsmokers, and hypertensive smokers. These data of high precision show that the relationship between serum cholesterol and CHD is not a threshold one, with increased risk confined to the two highest quintiles, but rather is a continuously graded one that powerfully affects risk for the great majority of middle-aged American men.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                19 July 2021
                July 2021
                : 13
                : 7
                : 1402
                Affiliations
                [1 ]Clinical Epidemiology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy; martina.spaziante@ 123456uniroma1.it (M.S.); enrico.girardi@ 123456inmi.it (E.G.)
                [2 ]Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; elisa.biliotti@ 123456uniroma1.it
                [3 ]Task Force Anti-COVID, AORN San Giuseppe Moscati, 83100 Avellino, Italy
                [4 ]ASST Santi Paolo e Carlo, Clinic of Infectious and Tropical Diseases, Department of Health Sciences, University of Milan, 20122 Milan, Italy; giulia.marchetti@ 123456unimi.it (G.M.); antonella.darminio@ 123456unimi.it (A.d.M.)
                [5 ]Icona Foundation, 20145 Milan, Italy; alessandro.tavelli@ 123456fondazioneicona.org
                [6 ]Department of Infectious Diseases, La Sapienza University, Polo Pontino, 04100 Latina, Italy; miriam.lichtner@ 123456uniroma1.it
                [7 ]Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Policlinico Agostino Gemelli IRCCS, 00168 Rome, Italy; antonella.cingolani@ 123456unicatt.it
                [8 ]HIV/AIDS Clinical Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy; stefania.cicalini@ 123456inmi.it (S.C.); andrea.antinori@ 123456inmi.it (A.A.)
                [9 ]Division of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy; massimo.puoti@ 123456ospedaleniguarda.it
                [10 ]Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London WC1N 1EH, UK; a.cozzi-lepri@ 123456ucl.ac.uk
                Author notes
                Author information
                https://orcid.org/0000-0002-3793-2755
                https://orcid.org/0000-0002-0754-6917
                https://orcid.org/0000-0001-8182-5896
                https://orcid.org/0000-0003-0073-1789
                Article
                viruses-13-01402
                10.3390/v13071402
                8310285
                0729bef7-b1ad-42e2-b21e-abc85b50fcdc
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 10 June 2021
                : 13 July 2021
                Categories
                Article

                Microbiology & Virology
                hiv/hcv coinfected patients,hcv eradication,hcv genotype,lipid metabolism,antiretroviral treatment,darunavir/ritonavir

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