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      Recent Developments regarding Human Immunodeficiency Virus Infection and Stroke

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          Abstract

          Human immunodeficiency virus (HIV) infection is strongly associated with ischemic stroke in the young. Data obtained from the Nationwide Inpatient Sample in the United States show an increase in the number of stroke hospitalizations in the HIV-infected population despite an overall decrease in the number of stroke hospitalizations. Few data exist, however, that address the mechanism of HIV-associated stroke. Recent studies have demonstrated that HIV may infect the endothelium and alter cerebrovascular functions. Whether the proposed mechanism alters the stroke risk is undetermined. Epidemiological studies suggest that HIV-related stroke is associated with a risk factor profile that differs from the HIV-negative young stroke population in that HIV-associated strokes are less likely to have hypertension, diabetes, hyperlipidemia and smoking as risk factors. A large population-based study, moreover, suggests an association between antiretroviral therapy and increased cardio- and cerebrovascular risks. Specific antiretroviral agents such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been implicated in the metabolic syndrome, accelerated atherosclerosis and an increased risk for ischemic stroke. In addition to discussing these developments, this paper also discusses the implications of recent data for stroke prevention in HIV-infected patients.

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          Most cited references42

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          Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.

          The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.
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            Risk of myocardial infarction and vascular death after transient ischemic attack and ischemic stroke: a systematic review and meta-analysis.

            Whether stroke patients should be investigated for asymptomatic coronary artery disease remains matter of debate. Absolute risks of myocardial infarction (MI) and vascular death after a stroke have not been accurately assessed. We performed a systematic review and a meta-analysis to determine the risk of MI and nonstroke vascular death after transient ischemic attack (TIA) and ischemic stroke. Cohort studies of TIA or ischemic stroke patients were included if they were published between 1980 and March 2005, reported risk of MI and nonstroke vascular death, enrolled >100 patients, and had at least 1 year of follow-up. We included 39 studies in a total of 65,996 patients with mean follow-up of 3.5 years. Two reviewers independently carried out data extraction using a standardized form. Absolute annual risks were estimated through weighted meta-regressions with a random effect. To test the predictions of expected event rates derived from our analysis, we used individual patient data. The annual risks were 2.1% (CI 95%: 1.9 to 2.4) for nonstroke vascular death, 2.2% (1.7 to 2.7) for total MI, 0.9% (0.7 to 1.2) for nonfatal MI and 1.1% (0.8 to 1.5) for fatal MI. The time course of risk was linear. Estimated risks fitted well with observed risks at the individual level. There was no heterogeneity in the absolute risks according to baseline study characteristics. Patients with TIA or stroke have a relatively high risk of MI and nonstroke vascular death. Additional research is needed to identify the determinants of coronary artery disease in stroke patients.
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              Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

              The distribution of risk factors for cardiovascular disease in patients aged 35-44 years who were treated for human immunodeficiency virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease inhibitor-containing regimen (n=223), compared with HIV-1-uninfected men (n=527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level, a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR], 1.20) and women (RR, 1.59; P<10(-6) for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy, risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered for all patients who have them.
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                Author and article information

                Journal
                CED
                Cerebrovasc Dis
                10.1159/issn.1015-9770
                Cerebrovascular Diseases
                S. Karger AG
                1015-9770
                1421-9786
                2012
                May 2012
                19 January 2012
                : 33
                : 3
                : 209-218
                Affiliations
                aUniversity of South Carolina, Columbia, S.C., bMayo Clinic, Rochester, Minn., cColumbia University, New York, N.Y., and dUniversity of North Carolina, Chapel Hill, N.C., USA
                Author notes
                *Prof. Souvik Sen, MD, MS, MPH, FAHA, University of South Carolina School of Medicine, 8 Medical Park Drive, Suite 420, Columbia, SC 29203 (USA), Tel. +1 803 545 6073, E-Mail souvik.sen@uscmed.sc.edu
                Article
                335300 Cerebrovasc Dis 2012;33:209–218
                10.1159/000335300
                22261608
                bf89b71b-fd8c-45b4-b822-51c2ba92a20e
                © 2012 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 30 May 2011
                : 17 November 2011
                Page count
                Tables: 3, Pages: 10
                Categories
                Review

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Stroke,Protease inhibitor,Antiretroviral therapy,Human immunodeficiency virus,Non-nucleoside reverse transcriptase inhibitors

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