Changes in plasma lipidome following initiation of antiretroviral therapy

Janine M. Trevillyan, Gerard Wong, Rebekah Puls, Kathy Petoumenos, Sean Emery, Natalie A. Mellett, Piyushkumar A. Mundra, Peter J. Meikle, Jennifer F. Hoy, for the ALTAIR Study Group

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Introduction HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease and important changes in lipid metabolism. Advances in mass-spectrometry technology allow for the detailed assessment of individual lipid species which may illuminate the mechanisms underlying increased cardiovascular risk. We describe the change in plasma lipidome with initiation of antiretroviral therapy and compare these by regimen. Methods Plasma lipid profiling (by electrospray isonisation-tandem mass spectrometry) was performed on ARV-naive HIV positive participants randomised to one of three regimens; tenofovir/emtricitabine with efavirenz, ritonavir-boosted atazanavir (atazanavir/r) or zidovudine/ abacavir. Participants (n = 115) who remained on their randomised regimen with complete samples available at baseline, week 12 and 48 were included. 306 lipid species from 22 lipid classes were analysed. Results Initiation of ART led to significant changes in lipidome which were partly dependent on the randomised regimen received. This led to significant differences in 72 lipid species and 7 classes (cholesterol ester, free cholesterol, phosphatidylcholine, GM3 ganglioside, trihexosylceramide, monohexosylceramide, and ceramides) by arm at week 48. Consistently higher lipid concentrations were seen with efavirenz compared with atazanavir/r or zidovudine/abacavir. Twelve of the lipid species and two lipid classes (cholesterol esters and ceramides) that were significantly increased in the efavirenz arm compared with the atazanavir/ r or zidovudine/abacavir arms have previously been associated with future cardiovascular events in HIV positive patients. Change in HIV viral load was predictive of change in 3 lipid species. Conclusions Initiation of ART lead to significant changes in the plasma lipidome that were greatest in those receiving efavirenz.
Original languageEnglish
Number of pages16
JournalPLoS ONE
Volume13
Issue number8
DOIs
Publication statusPublished - 1 Aug 2018

Cite this

Trevillyan, J. M., Wong, G., Puls, R., Petoumenos, K., Emery, S., Mellett, N. A., ... for the ALTAIR Study Group (2018). Changes in plasma lipidome following initiation of antiretroviral therapy. PLoS ONE, 13(8). https://doi.org/10.1371/journal.pone.0202944
Trevillyan, Janine M. ; Wong, Gerard ; Puls, Rebekah ; Petoumenos, Kathy ; Emery, Sean ; Mellett, Natalie A. ; Mundra, Piyushkumar A. ; Meikle, Peter J. ; Hoy, Jennifer F. ; for the ALTAIR Study Group. / Changes in plasma lipidome following initiation of antiretroviral therapy. In: PLoS ONE. 2018 ; Vol. 13, No. 8.
@article{e1a1fc1581e749df8dbea3b06875e426,
title = "Changes in plasma lipidome following initiation of antiretroviral therapy",
abstract = "Introduction HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease and important changes in lipid metabolism. Advances in mass-spectrometry technology allow for the detailed assessment of individual lipid species which may illuminate the mechanisms underlying increased cardiovascular risk. We describe the change in plasma lipidome with initiation of antiretroviral therapy and compare these by regimen. Methods Plasma lipid profiling (by electrospray isonisation-tandem mass spectrometry) was performed on ARV-naive HIV positive participants randomised to one of three regimens; tenofovir/emtricitabine with efavirenz, ritonavir-boosted atazanavir (atazanavir/r) or zidovudine/ abacavir. Participants (n = 115) who remained on their randomised regimen with complete samples available at baseline, week 12 and 48 were included. 306 lipid species from 22 lipid classes were analysed. Results Initiation of ART led to significant changes in lipidome which were partly dependent on the randomised regimen received. This led to significant differences in 72 lipid species and 7 classes (cholesterol ester, free cholesterol, phosphatidylcholine, GM3 ganglioside, trihexosylceramide, monohexosylceramide, and ceramides) by arm at week 48. Consistently higher lipid concentrations were seen with efavirenz compared with atazanavir/r or zidovudine/abacavir. Twelve of the lipid species and two lipid classes (cholesterol esters and ceramides) that were significantly increased in the efavirenz arm compared with the atazanavir/ r or zidovudine/abacavir arms have previously been associated with future cardiovascular events in HIV positive patients. Change in HIV viral load was predictive of change in 3 lipid species. Conclusions Initiation of ART lead to significant changes in the plasma lipidome that were greatest in those receiving efavirenz.",
author = "Trevillyan, {Janine M.} and Gerard Wong and Rebekah Puls and Kathy Petoumenos and Sean Emery and Mellett, {Natalie A.} and Mundra, {Piyushkumar A.} and Meikle, {Peter J.} and Hoy, {Jennifer F.} and {for the ALTAIR Study Group}",
year = "2018",
month = "8",
day = "1",
doi = "10.1371/journal.pone.0202944",
language = "English",
volume = "13",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

Trevillyan, JM, Wong, G, Puls, R, Petoumenos, K, Emery, S, Mellett, NA, Mundra, PA, Meikle, PJ, Hoy, JF & for the ALTAIR Study Group 2018, 'Changes in plasma lipidome following initiation of antiretroviral therapy' PLoS ONE, vol. 13, no. 8. https://doi.org/10.1371/journal.pone.0202944

Changes in plasma lipidome following initiation of antiretroviral therapy. / Trevillyan, Janine M.; Wong, Gerard; Puls, Rebekah; Petoumenos, Kathy; Emery, Sean; Mellett, Natalie A.; Mundra, Piyushkumar A.; Meikle, Peter J.; Hoy, Jennifer F.; for the ALTAIR Study Group.

In: PLoS ONE, Vol. 13, No. 8, 01.08.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Changes in plasma lipidome following initiation of antiretroviral therapy

AU - Trevillyan, Janine M.

AU - Wong, Gerard

AU - Puls, Rebekah

AU - Petoumenos, Kathy

AU - Emery, Sean

AU - Mellett, Natalie A.

AU - Mundra, Piyushkumar A.

AU - Meikle, Peter J.

AU - Hoy, Jennifer F.

AU - for the ALTAIR Study Group

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Introduction HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease and important changes in lipid metabolism. Advances in mass-spectrometry technology allow for the detailed assessment of individual lipid species which may illuminate the mechanisms underlying increased cardiovascular risk. We describe the change in plasma lipidome with initiation of antiretroviral therapy and compare these by regimen. Methods Plasma lipid profiling (by electrospray isonisation-tandem mass spectrometry) was performed on ARV-naive HIV positive participants randomised to one of three regimens; tenofovir/emtricitabine with efavirenz, ritonavir-boosted atazanavir (atazanavir/r) or zidovudine/ abacavir. Participants (n = 115) who remained on their randomised regimen with complete samples available at baseline, week 12 and 48 were included. 306 lipid species from 22 lipid classes were analysed. Results Initiation of ART led to significant changes in lipidome which were partly dependent on the randomised regimen received. This led to significant differences in 72 lipid species and 7 classes (cholesterol ester, free cholesterol, phosphatidylcholine, GM3 ganglioside, trihexosylceramide, monohexosylceramide, and ceramides) by arm at week 48. Consistently higher lipid concentrations were seen with efavirenz compared with atazanavir/r or zidovudine/abacavir. Twelve of the lipid species and two lipid classes (cholesterol esters and ceramides) that were significantly increased in the efavirenz arm compared with the atazanavir/ r or zidovudine/abacavir arms have previously been associated with future cardiovascular events in HIV positive patients. Change in HIV viral load was predictive of change in 3 lipid species. Conclusions Initiation of ART lead to significant changes in the plasma lipidome that were greatest in those receiving efavirenz.

AB - Introduction HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease and important changes in lipid metabolism. Advances in mass-spectrometry technology allow for the detailed assessment of individual lipid species which may illuminate the mechanisms underlying increased cardiovascular risk. We describe the change in plasma lipidome with initiation of antiretroviral therapy and compare these by regimen. Methods Plasma lipid profiling (by electrospray isonisation-tandem mass spectrometry) was performed on ARV-naive HIV positive participants randomised to one of three regimens; tenofovir/emtricitabine with efavirenz, ritonavir-boosted atazanavir (atazanavir/r) or zidovudine/ abacavir. Participants (n = 115) who remained on their randomised regimen with complete samples available at baseline, week 12 and 48 were included. 306 lipid species from 22 lipid classes were analysed. Results Initiation of ART led to significant changes in lipidome which were partly dependent on the randomised regimen received. This led to significant differences in 72 lipid species and 7 classes (cholesterol ester, free cholesterol, phosphatidylcholine, GM3 ganglioside, trihexosylceramide, monohexosylceramide, and ceramides) by arm at week 48. Consistently higher lipid concentrations were seen with efavirenz compared with atazanavir/r or zidovudine/abacavir. Twelve of the lipid species and two lipid classes (cholesterol esters and ceramides) that were significantly increased in the efavirenz arm compared with the atazanavir/ r or zidovudine/abacavir arms have previously been associated with future cardiovascular events in HIV positive patients. Change in HIV viral load was predictive of change in 3 lipid species. Conclusions Initiation of ART lead to significant changes in the plasma lipidome that were greatest in those receiving efavirenz.

UR - http://www.scopus.com/inward/record.url?scp=85052806683&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0202944

DO - 10.1371/journal.pone.0202944

M3 - Article

VL - 13

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

ER -