Prospective Analysis of Lipid Composition Changes with Antiretroviral Therapy and Immune Activation in Persons Living with HIV

Martha A. Belury, Emily Bowman, Janelle Gabriel, Brandon Snyder, Manjusha Kulkarni, Marilly Palettas, Xiaokui Mo, Jordan E. Lake, David Zidar, Scott F. Sieg, Benigno Rodriguez, Martin P. Playford, Adriana Andrade, Daniel R. Kuritzkes, Nehal N. Mehta, Michael M. Lederman, Nicholas Funderburg

Abstract


Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lysophosphatidylcholine, LPC) and their saturated (SaFA), monounsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described.

Methods: Plasma lipid concentrations and their fatty acid composition were measured by differential mobility spectroscopy in samples from 35 treatment-naive HIV+ participants beginning raltegravir (RAL)-based ART and from HIV- individuals (N=13) matched for age and sex.

Results: The levels of SaFA, including palmitic (16:0) and stearic (18:0) acid were enriched in HIV+ participants (pre- and post-ART), and SaFA levels were often positively correlated with levels of immune activation (ie, IL-6, sCD14, and TNFR1) at baseline and week 48. Levels of PUFAs (including 18:3, 20:4, and 20:5) were lower in HIV+ participants at baseline compared to levels in HIV- participants (P<0.01), and levels of these PUFAs were increased following 48 weeks of ART. Levels of PUFAs were often inversely related to immune activation. Levels of LPC were increased in HIV+ participants, both pre- and post-ART vs HIV- participants, and the composition of LPC was enriched for SaFAs among HIV+ individuals. At week 48, several LPC molecules containing SaFAs were positively correlated with levels of sCD14, D-dimer, and TNFR1 (P<0.01), and levels of PUFA-containing LPC (18:3, 20:5, 22:5, 22:6) were positively correlated with CD4+ T cell counts and inversely correlated with sCD14 and IL-6 (P<0.01).

Conclusions: The composition of the lipidome is altered in HIV infection and changes when ART is administered. Alterations in SaFAs were generally associated with inflammatory markers and may contribute to comorbid disease pathogenesis.


Keywords


lysophosphatidylcholine, immune activation, antiretroviral therapy, fatty acids

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