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      Sleep Disordered Breathing, Fatigue, and Sleepiness in HIV-Infected and -Uninfected Men

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          Abstract

          Study Objectives

          We investigated the association of HIV infection and highly active antiretroviral therapy (HAART) with sleep disordered breathing (SDB), fatigue, and sleepiness.

          Methods

          HIV-uninfected men (HIV−; n = 60), HIV-infected men using HAART (HIV+/HAART+; n = 58), and HIV-infected men not using HAART (HIV+/HAART−; n = 41) recruited from two sites of the Multicenter AIDS cohort study (MACS) underwent a nocturnal sleep study, anthropometric assessment, and questionnaires for fatigue and the Epworth Sleepiness Scale. The prevalence of SDB in HIV- men was compared to that in men matched from the Sleep Heart Health Study (SHHS).

          Results

          The prevalence of SDB was unexpectedly high in all groups: 86.7% for HIV−, 70.7% for HIV+/HAART+, and 73.2% for HIV+/HAART−, despite lower body-mass indices (BMI) in HIV+ groups. The higher prevalence in the HIV− men was significant in univariate analyses but not after adjustment for BMI and other variables. SDB was significantly more common in HIV− men in this study than those in SHHS, and was common in participants with BMIs <25 kg/m 2. HIV+ men reported fatigue more frequently than HIV− men (25.5% vs. 6.7%; p = 0.003), but self-reported sleepiness did not differ among the three groups. Sleepiness, but not fatigue, was significantly associated with SDB.

          Conclusions

          SDB was highly prevalent in HIV− and HIV+ men, despite a normal or slightly elevated BMI. The high rate of SDB in men who have sex with men deserves further investigation. Sleepiness, but not fatigue, was related to the presence of SDB. Clinicians caring for HIV-infected patients should distinguish between fatigue and sleepiness when considering those at risk for SDB, especially in non-obese men.

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          Most cited references32

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          Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.

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            A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors.

            To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. Cross-sectional study. Outpatient clinic of a university teaching hospital. HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47). Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed. HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.
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              Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard.

              Excessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean+/-2 SD or by the 2.5 and 97.5 percentiles. The 'rule of thumb' that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug-free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                3 July 2014
                : 9
                : 7
                : e99258
                Affiliations
                [1 ]Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
                [2 ]Division of Endocrinology and Metabolism, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
                [3 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [4 ]Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                University of Kansas Medical Center, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SPP TTB LPJ JBM AL LJH RG JJ SR ARS PLS. Performed the experiments: SPP TTB LPJ JBM AL LJH RG JJ SR ARS PLS. Analyzed the data: SPP TTB LPJ JBM AL LJH RG JJ SR ARS PLS. Wrote the paper: SPP TTB LPJ JBM AL LJH RG JJ SR ARS PLS.

                Article
                PONE-D-13-30043
                10.1371/journal.pone.0099258
                4084642
                24991815
                4454f451-3f22-43f7-9c31-132a05ee8298
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 July 2013
                : 12 May 2014
                Page count
                Pages: 11
                Funding
                This work was supported through NIH grants RO1-HL07955, K23-HL77137, K23-AT2862, UL1-RR-025005 (Johns Hopkins Institute for Clinical and Translational Research; ICTR), U01-AI-35042 (MACS - Baltimore site), U01-AI-35041 (MACS - Pittsburgh site), and U01-AI-35043 (CAMACS). The Baltimore site of the SHHS was supported by the National Heart, Lung, and Blood Institute cooperative agreement U01HL53937. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                Nutrition
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and health sciences
                Diagnostic medicine
                HIV clinical manifestations
                HIV diagnosis and management
                Epidemiology
                Clinical epidemiology
                HIV epidemiology
                Infectious disease epidemiology
                Infectious Diseases
                Viral Diseases
                Neurology
                Sleep Disorders
                Pulmonology
                Research and Analysis Methods
                Research Design
                Clinical Research Design

                Uncategorized
                Uncategorized

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