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      Association between lipodystrophy and length of exposure to ARTs in adult HIV-1 infected patients in Montreal

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          Abstract

          Background

          The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs.

          Method

          We conducted a cross sectional study in all HIV- infected patients attending the HIV clinic in the Centre hospitalier universitaire de Montréal (CHUM) with DEXA scan. Lipodystrophy was defined as a trunk/limb fat ratio ≥ 1.5. Association between cumulative exposure to antiretroviral (measured in years of use) with trunk/limb fat ratio (coded as a continuous variable) was assessed using univariate and multivariate linear regression for each antiretroviral drug with at least 40 exposed patients.

          Results

          One hundred sixty-six patients were included. Seventy-five percent were male, median age was 56 years, 67% were Caucasian. Overall, prevalence of lipodystrophy was 47%, with a mean trunk/limb fat ratio of 1.87, SD = 1.03, min = 0.6 and max = 5.87. Each 10-year increase in age and HIV infection duration was associated with an average increase of 0.24 and 0.34 for the trunk/limb fat ratio respectively. ( p = 0.003, p = 0.002, respectively) Patients classified as lipodystrophic were more likely to be diabetic (50 vs. 28%, p = 0.07) and to have dyslipidemia (47 vs. 19%, p = 0.01). According to viral load at DEXA test, each one log increase was associated with less probability (0.7) of lipodystrophy. (p = 0.01) Among ARV drugs tested, there was an association between years of use of d4T, ritonavir and raltegravir and higher trunk/limb fat ratio (indicating more lipodystrophy) ( p < 0.05).

          Conclusion

          Lipodystrophy is very common in HIV infected patients and is correlated with duration of some new antiretroviral drugs.

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          Most cited references20

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          Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study.

          The prevalence and severity of lipodystrophy syndrome with long-term therapy for HIV-1 infection that includes a protease inhibitor is unknown. We studied the natural course of the syndrome to develop diagnostic criteria and identifying markers that predict its severity. We assessed 113 patients who were receiving HIV-1 protease inhibitors (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) never treated with a protease inhibitor. Lipodystrophy was assessed by questionnaire (including patients' rating of severity), physical examination, and dual-energy x-ray absorptiometry. Body composition and fasting lipid and glycaemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. There was 98% concordance between patients' reports of the presence or absence of lipodystrophy (reported by 83% of protease-inhibitor recipients and 4% of treatment-naïve patients; p=0.0001) and physical examination. Patients' ratings of lipodystrophy were significantly associated with declining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease-inhibitor therapy and lower bodyweight before therapy, and more severe lipodystrophy was associated with higher previous (p < 0.03) and current (p < or = 0.01) triglyceride and C-peptide concentrations, and less peripheral and greater central fat (p=0.005 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months in protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naïve patients; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibitor recipients and diabetes mellitus in 7%; in all but three patients these abnormalities were detected on 2 h post-glucose load values. Diagnosis and rating severity of lipodystrophy is aided by the combination of physical examination, patient's rating, and measurement of body fat, fasting triglycerides, and C-peptide. Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict lipodystrophy severity. Lipodystrophy was common and progressive after almost 2 years of protease inhibitor therapy, but was not usually severe. Hyperlipidaemia and impaired glucose tolerance were also common.
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            Dramatic improvement in survival among adult Brazilian AIDS patients

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              Clinical assessment of HIV-associated lipodystrophy in an ambulatory population.

              To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. Eight clinics specializing in the care of HIV-1 infected patients. A total of 1077 patients were evaluated for signs of fat maldistribution. A standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis. Demographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy. Independent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use. HIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.
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                Author and article information

                Contributors
                ahalikhani@yahoo.com
                Helene.morin.chum@ssss.gouv.qc.ca
                Stephanie.matte.chum@ssss.gouv.qc.ca
                Pouriya.alikhani@mail.mcgill.ca
                c.tremblay@umontreal.ca
                514 890 8000 , madeleine.durand.chum@ssss.gouv.qc.ca
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                18 September 2019
                18 September 2019
                2019
                : 19
                : 820
                Affiliations
                [1 ]ISNI 0000 0001 2227 0923, GRID grid.411623.3, Department of infectious diseases &antimicrobial resistance research center, , Mazandaran University of Medical Sciences, ; Sari, Iran
                [2 ]CHUM-CRCHUM, Tour Saint-Antoine - 3e étage, local SO3-288, 850, rue Saint-Denis, Montréal, Québec H2X 0A9 Canada
                [3 ]ISNI 0000 0004 1936 8649, GRID grid.14709.3b, McGill Centre for bioinformatics, , McGill University, ; Montreal, Canada
                Article
                4446
                10.1186/s12879-019-4446-9
                6751890
                31533648
                bf46458e-6804-48ce-8b46-a9d2e304bc9b
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 October 2018
                : 6 September 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                hiv,antiretroviral therapy,lipodystrophy,risk factors,dyslipidemia

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