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

Citation: Kelesidis T, Tran TTT, Brown TT, Moser C, Ribaudo HJ, Dubé MP, Murphy RL, Yang O, McComsey GA, Stein JH, Currier JS. 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. Antivir Ther. 2017;22(2):113-126. doi: 10.3851/IMP3093. Epub 2016 Sep 23. PMID: 27661466. PMCID: PMC5364070. 

Access full article:

https://www.ncbi.nlm.nih.gov/pubmed/27661466

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-naive 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 analysed 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 time points 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.

Antivir Ther. 2017;22(2):113-126. doi: 10.3851/IMP3093. Epub 2016 Sep 23.

Categories

CRS
Topics

Clinical Trials

A5327: Sofosbuvir + Ribavirin w/o Interferon for Treatment...

A5327 SWIFT-C is a Phase I, open-label, two-cohort clinical trial, in which between 44 and 50 acutely HCV-infected HIV-1...

Read More

P2001 (DAIDS ID 12026): Evaluating the Pharmacokinetics,...

TB is a major cause of illness and death in women of reproductive age. Pregnant and postpartum women with latent TB are at...

Read More

The Pharmacokinetics, Safety and Acceptability of New...

PK, safety and acceptability data and practical guidance on the optimal dosing of new more child-friendly formulations of...

Read More

A5324: A Randomized, Double-Blinded, Placebo-Controlled...

ACTG A5324 is a phase IV randomized, double-blinded, placebo-controlled study to assess the efficacy of adding Maraviroc (MVC)...

Read More

A5302:  BioBank for Surrogate Marker Research for TB...

Primary Objective To obtain sputum, serum, urine, and peripheral blood mononuclear cells (PBMCs) for central TB biorepository...

Read More