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      Altered Lipid Profiles and Vaccine Induced-Humoral Responses in Children Living With HIV on Antiretroviral Therapy in Tanzania

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          Abstract

          People living with HIV, even under therapy, have a high burden of age-related co-morbidities including an increased risk of dyslipidemia (which often predisposes to cardiovascular diseases) and immune-aging. In this study, lipid profiles and antibody responses to measles and pertussis toxin vaccines were compared between ART experienced HIV+ children (n=64) aged 5-10 years, and their age- and sex-matched HIV- controls (n=47). Prevalence of high-density lipoprotein cholesterol (HDL-c) and triglyceride-driven dyslipidemia was higher among treated HIV+ children than in controls (51.6% vs 27.7% respectively, p < 0.019). In a multivariate Poisson regression model adjusted for age, sex and BMI, the association between low HDL-c, hypertriglyceridemia and HIV remained significantly high (for HDL-c: ARR: 0.89, 95% CI: 0.82 – 0.96, p = 0.003; for triglycerides: ARR: 1.54, 95% CI: 1.31 – 1.81, p < 0.001). Among HIV+ children, the use of lopinavir/ritonavir, a protease-based antiretroviral therapy was also associated elevation of triglyceride levels (p = 0.032). Also, HIV+ children had a 2.8-fold reduction of anti-measles IgG titers and 17.1-fold reduction of anti-pertussis toxin IgG levels when compared to HIV- children. Our findings suggest that dyslipidemia and inadequate vaccine-induced antibody responses observed in this population of young African HIV+ children might increase their risk for premature onset of cardiovascular illnesses and acquisition of preventable diseases.

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          Most cited references54

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          Premature age-related comorbidities among HIV-infected persons compared with the general population.

          Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects. We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp. There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/μL (OR, 4.46), and ART exposure (OR, 1.01). Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors. These data support the need for earlier screening for NICMs in HIV-infected patients.
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            Aging of the immune system: Focus on inflammation and vaccination.

            Major advances in preventing, delaying, or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching eight to nine decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and loss of function typical of older individuals is a major challenge in current aging research. Among the possible causes, an impairment of the immune system plays a major role, and indeed numerous studies have described immunological changes which occur with age. Far from the intention of being exhaustive, this review will focus on recent advances and views on the role that modifications of cell signalling and remodelling of the immune response play during human aging and longevity, paying particular attention to phenomena which are linked to the so called inflammaging process, such as dysregulation of innate immunity, altered T-cell or B-cell maturation and differentiation, as well as to the implications of immune aging for vaccination strategies in the elderly.
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              HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction.

              Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants. We assessed the association between HIV and incident AMI within CVDRF strata.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                09 November 2021
                2021
                : 11
                : 721747
                Affiliations
                [1] 1 National Institute for Medical Research (NIMR), Mbeya Medical Research Centre (MMRC) , Mbeya, Tanzania
                [2] 2 Department of Internal Medicine, Mbeya Zonal Referral Hospital and University of Dar es Salaam Mbeya College of Health and Allied Sciences , Mbeya, Tanzania
                [3] 3 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara , Ferrara, Italy
                [4] 4 Department of Radiology, Mbeya Zonal Referral Hospital and University of Dar es Salaam Mbeya College of Health and Allied Sciences , Mbeya, Tanzania
                [5] 5 Department of Paediatric, Mbeya Zonal Referral Hospital and University of Dar es Salaam Mbeya College of Health and Allied Sciences , Mbeya, Tanzania
                [6] 6 Department of Microbiology and Immunology, University of Dar es Salaam - Mbeya College of Health and Allied Sciences (UDSM-MCHAS) , Mbeya, Tanzania
                Author notes

                Edited by: Ilhem Messaoudi, University of California, Irvine, United States

                Reviewed by: Michael Z. Zulu, University of California, Irvine, United States; J. Zachary Porterfield, University of Kentucky, United States

                *Correspondence: Mkunde Chachage, chachage.mkunde@ 123456udsm.ac.tz ; Wilbert Mbuya, wmbuya@ 123456nimr-mmrc.org

                This article was submitted to Virus and Host, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2021.721747
                8630663
                8f33934b-e231-4fcc-8091-40e4fa78eb43
                Copyright © 2021 Mbuya, Mwakyula, Olomi, Agrea, Nicoli, Ngatunga, Mujwahuzi, Mwanyika and Chachage

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 June 2021
                : 13 October 2021
                Page count
                Figures: 5, Tables: 4, Equations: 0, References: 55, Pages: 11, Words: 5225
                Funding
                Funded by: University of Dar es Salaam , doi 10.13039/100012907;
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                hiv,children,dyslipidemia,cardiovascular disease,immune senescence,childhood vaccines,art

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