Treatment of HIV Infection with a Raltegravir-Based Regimen Increases LDL Levels, but Improves HDL Cholesterol Efflux Capacity

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.

Good Fences Make Good Neighbors: Human Immunodeficiency Virus and Vascular Disease

“…The classes of drugs most commonly implicated are protease inhibitors. The majority of inflammatory and cardiovascular disease biomarkers show a decline with effective therapy, however, confirming a benefit of ART even for cardiovascular disease outcomes [90, 95–97].…”

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

“…Here, in a substudy of the AIDS Clinical Trials Group (ACTG) trials A5248/A5249s [27–30], using liquid chromatography tandem mass spectrometry (LC MS/ MS; Complex Lipid Panel, Metabolon), we examined the concentrations and fatty acid composition of lipid classes in plasma samples: 1) longitudinally in ART-naive HIV+ adults who initiated an ART regimen containing raltegravir (RAL), tenofovir (TDF), and emtricitabine (FTC), and 2) in samples from a single time point in an age and sex similar HIV- population. We hypothesized that infection with HIV and treatment with ART would alter the composition of the lipidome, and that these changes would be associated with markers of inflammation.…”

Reduction of Immune Activation and Partial Recovery of Staphylococcal Enterotoxin B-Induced Cytokine Production After Switching to an Integrase Strand Transfer Inhibitor-Containing Regimen: Results from an Observational Cohort Study

“…The reasons behind this further decline in T lymphocyte activation burden in patients with long-term viral suppression are still unclear. One hypothesis is that the INSTI class may decrease inflammation and immune activation more than other antiretroviral classes because of their positive effects on lipid profiles, in particular on highdensity lipoprotein cholesterol efflux capacity and oxidized low-density lipoprotein [30], known to be related to markers of monocyte activation that predict mortality [31]. This hypothesis, however, seems unlikely in our cohort because (1) we failed to find changes in lipid metabolism; and (2) we did not observe any modification in sCD14.…”