Treatment of HIV infection with a raltegravir-based regimen increases LDL levels, but improves HDL cholesterol efflux capacity.

TitleTreatment of HIV infection with a raltegravir-based regimen increases LDL levels, but improves HDL cholesterol efflux capacity.
Publication TypeJournal Article
Year of Publication2017
AuthorsFunderburg NT, Xu D, Playford MP, Joshi AA, Andrade A, Kuritzkes DR, Lederman MM, Mehta NN
JournalAntivir Ther
Volume22
Issue1
Pagination71-75
Date Published2017
ISSN2040-2058
KeywordsAdult, Anti-HIV Agents, Biological Transport, Active, Cholesterol, HDL, Emtricitabine, Female, HIV Infections, Humans, Lipoproteins, LDL, Male, Middle Aged, Raltegravir Potassium, RNA, Viral, Tenofovir, Young Adult
Abstract

BACKGROUND: Persons infected with HIV often have altered lipid profiles that may be affected by antiretroviral therapies (ART). Traditional lipid measurements may be insufficient to assess cardiovascular disease (CVD) risk in this population.

METHODS: We report results from 39 ART-naive participants in a substudy of A5248, a single-arm study of raltegravir, emtricitabine/tenofovir administration. Samples were collected at baseline, 12, 24 and 48 weeks after ART initiation. We performed advanced lipid phenotyping using nuclear magnetic resonance spectroscopy (Liposcience, Raleigh, NC, USA) for lipid particle size and number, and examined high-density lipoprotein (HDL) function measuring reverse cholesterol transport using J774 macrophages.

RESULTS: We report significant increases in total cholesterol (13 mg/dl; P<0.001) and low-density lipoprotein (LDL; 8 mg/dl; P=0.03), with no change in triglycerides and without an increase in LDL particle number (P>0.1 all time points). HDL levels were increased over baseline levels at all time points (P<0.003), but reached a peak at week 12 and subsequently declined. HDL particle numbers also increased from baseline (P<0.002) and HDL function improved at week 48 (7% increase in efflux capacity; P<0.001). Oxidized LDL (oxLDL) levels decreased by week 12, but rose subsequently, and were not different from baseline at later time points.

CONCLUSIONS: HDL increases were associated with increases in beneficial HDL particles and HDL cholesterol efflux capacity, which may reduce future CVD events. Persistent inflammation in these HIV+ participants, may be a cause or consequence of oxLDL levels, and may contribute to declining levels of HDL over time. Clinicaltrials.gov NCT00660972.

DOI10.3851/IMP3091
Alternate JournalAntivir. Ther. (Lond.)
PubMed ID27740536
PubMed Central IDPMC5516727
Grant ListR00 HL108743 / HL / NHLBI NIH HHS / United States
R24 AI067039 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
R56 HL126563 / HL / NHLBI NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States