Plasma lipidome abnormalities in people with HIV initiating antiretroviral therapy
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(2020) 5:26
Translational Medicine Communications
RESEARCH
Open Access
Plasma lipidome abnormalities in people with HIV initiating antiretroviral therapy Emily R. Bowman1* , Manjusha Kulkarni1, Janelle Gabriel1, Xiaokui Mo1, Brett Klamer1, Martha Belury1, Jordan E. Lake2, David Zidar3, Scott F. Sieg3, Nehal N. Mehta4, Martin P. Playford4, Daniel R. Kuritzkes5, Adriana Andrade6, Elizabeth Koss Schmidt1, Christopher Taylor1, Edgar T. Overton7, Amanda L. Willig7, Michael M. Lederman3, Nicholas T. Funderburg1 and the AIDS Clinical Trials Group A5248/A5249s Team
Abstract Background: Dyslipidemia often accompanies human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART). Lipid abnormalities likely contribute to increased cardiometabolic disease among people with HIV (PWH). Here, we expand our previous findings on changes in the lipidome following ART initiation, and associations among lipid species, including ceramides (CER), diacylglycerols (DAG), and triacylglycerols (TAG), with immune activation. Methods: Concentrations and fatty acid composition of plasma lipids (~ 1300 species) were measured by differential mobility spectroscopy in samples from 35 treatment-naïve PWH pre- and post-initiation of ART (raltegravir (RAL)/ tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)); lipidomes were compared to those found in demographically similar HIV-uninfected individuals (n = 13). Results: Compared to people without HIV, 37.1% of all lipid species measured were altered in PWH at baseline, and 31.8% of lipid species were altered following 48 weeks of ART. Concentrations of lipid classes were also altered in PWH; diacylglycerols (DAGs) and triacylglycerols (TAGs) were increased at baseline, and DAGs remained increased after 48 weeks of ART. Lipids previously linked to cardiovascular disease (CVD) and diabetes were enriched in PWH pre- and post ART, and were related to immune activation and insulin resistance scores. Polyunsaturated fatty acid (PUFA)containing lipids were lower in PWH compared to levels in controls, and were inversely related to levels of inflammatory biomarkers. Conclusions: HIV infection and ART initiation both induce cardiometabolic changes to the composition of the plasma lipidome. These alterations are associated with inflammatory biomarkers, and may directly contribute to elevated CVD risk and diabetes. Trial registration: This study is registered with Clinicaltrials.gov (NCT00660972). Registered April 16, 2008. Keywords: Lipidome, HIV, Antiretroviral therapy, Inflammation, Cardiovascular disease
* Correspondence: [email protected] 1 The Ohio State University, 333 W. 10th Ave. 5198 Graves Hall, Columbus, OH 43210, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and
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