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

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, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (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.

Macrophage maturation from blood monocytes is altered in people with HIV, and is linked to serum lipid profiles and activation indices: A model for studying atherogenic mechanisms

“…The underlying drivers of increased innate immune activation in MDMs from PWH are myriad and include microbial translocation, coinfections, and inflammatory lipid profiles [72]. Previous studies have linked lipid species and lipid classes to markers of immune activation in PWH [36,38,72]. Here, this work extends those findings and provides multidimensional associations among the lipidome, inflammatory markers, and MDM transcriptional and functional profiles.…”

“…Pooled serum from HIV+ ART+ donors was enriched for SaFAs, containing significantly elevated concentrations of myristic acid (14:0), palmitic acid (16:0), margaric acid (17:0), and stearic acid (18:0) compared to levels of these lipids in HIV-pooled serum (S7A and S7B Fig). SaFAs promote inflammation [39], and are associated with immune activation in HIV infection [36]. Pooled serum from HIV+ donors also had decreased levels of anti-inflammatory PUFAs [44,45].…”

“…Certain lipid classes and lipid species are associated with CVD in PWH and in the general population, and may drive vascular inflammation and myeloid cell activation [27,[35][36][37][38][39]. Elevated https://doi.org/10.1371/journal.ppat.1008869.g002…”

Changes in plasma lipidome following initiation of antiretroviral therapy

“…Our finding of changes in plasma lipidome with initiation of ART are supported by that of Belury et.al. who demonstrated in a similar demographic of ARV naïve HIV positive individuals that initiation of ART with a raltegravir based regimen led to significant changes in the proportional representation of saturated, monounsaturated and polyunsaturated fatty acids [ 34 ]. Of interest they identified increases in a number of lysophosphatidylcholine lipid species (specifically LPC 10:0 and LPC 20:0) with ART initiation which was also seen in all arms of our study, with no difference across arms, suggesting that these changes are not specific to an ARV class and thus may be secondary to changes in HIV driven inflammation and innate immune function.…”

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

“…There is a growing appreciation that traditional lipid measurements (low-density lipoprotein, high-density lipoprotein, and total cholesterol) may inadequately capture dyslipidemia and CVD risk in PWH receiving ART. 56 Members of the Funderburg group 57,58 and others 59 have recently reported substantial differences in lipid classes and lipid species in PWH and uninfected populations, even when traditional lipid measurements between these groups were not different. These advanced lipid analyses have also linked alterations in the lipidome to inflammation, monocyte activation, and atherosclerosis.…”