Changes in plasma levels of oxidized lipoproteins and lipoprotein subfractions with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy and associations with common carotid artery intima-media thickness: ACTG 5260s.

TitleChanges in plasma levels of oxidized lipoproteins and lipoprotein subfractions with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy and associations with common carotid artery intima-media thickness: ACTG 5260s.
Publication TypeJournal Article
Year of Publication2016
AuthorsKelesidis T, Tran TTien T, Brown TT, Moser C, Ribaudo HJ, Dubé MP, Yang OO, McComsey GA, Stein JH, Currier JS
JournalAntivir Ther
Date Published2016 Sep 23
ISSN2040-2058
Abstract

BACKGROUND: The role of oxidized lipoproteins (high-density [HDLox] and low-density [LDLox]) and total lipoprotein particle (Lp) number and size in HIV-related cardiovascular disease (CVD) is unclear. The goal of this study was to evaluate changes of these biomarkers and their associations with rate of carotid intima media thickness progression over 3 years (ΔCIMT) in chronic HIV infection.

METHODS: Prospective study of 234 HIV-infected antiretroviral treatment naïve participants without CVD who were randomized to receive tenofovir-emtricitabine plus atazanavir/ritonavir, darunavir/ ritonavir, or raltegravir (RAL) and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter. Biomarker changes over 24, 48 or 96 weeks from baseline and pairwise treatment group comparisons were examined. Associations of these biomarkers with ΔCIMT were analyzed with mixed effects linear regression.

RESULTS: HDLp number increased with both protease inhibitors (PIs) over 48 weeks, while LDLp number declined with RAL; Lp size did not change. Over 96 weeks, normalized HDLox declined with both PIs; LDLox increased in all groups. Few treatment group differences were observed across all biomarkers. Associations between ΔCIMT and oxidized lipoproteins at all timepoints were not apparent (p≥0.10). There was some evidence of slower ΔCIMT for higher HDLp number (p=0.06) and for lower LDLp number (p=0.08) measured at baseline.

CONCLUSIONS: Unexpectedly, LDLox increased modestly in all treatment groups after ART initiation. Associations of plasma HDLox and LDLox with ΔCIMT were not apparent. While plasma levels of abnormal lipoproteins have been shown to be associated with CVD outcomes, clear associations with sub-clinical atherosclerosis progression were not apparent in our study.

DOI10.3851/IMP3093
Alternate JournalAntivir. Ther. (Lond.)
PubMed ID27661466
Grant ListK24 AI056933 / AI / NIAID NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
K08 AI108272 / AI / NIAID NIH HHS / United States
R01 HL095126 / HL / NHLBI NIH HHS / United States
R01 HL095132 / HL / NHLBI NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI069471 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States