Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

Citation: Kelesidis T, Tran TTT, Brown TT,  Moser C,  Ribaudo HJ,  Dubé MP, Murphy RL, Yang O,  McComsey GA, Stein JH, Currier  JS. Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection. AIDS. 2016 Nov 13;30(17):2625-2633. PMID: 27603288. PMCID: PMC5083154.

Access full article:

https://www.ncbi.nlm.nih.gov/pubmed/27603288

OBJECTIVE:
The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized HDL and LDL (HDLox and LDLox) contribute to HIV-1-related immune dysfunction.

STUDY:
In the AIDS Clinical Trials Group A5260, 234 HIV-infected antiretroviral therapy (ART)-naive participants were randomized to receive tenofovir-emtricitabine and protease inhibitors or raltegravir and had HIV-1 RNA less than 50 copies/ml by week 24 and thereafter.

METHODS:
Associations between biomarkers of inflammation (IL-6, high-sensitivity C-reactive protein and D-dimer), immune activation (sCD163, sCD14, soluble IL-2 receptor, CD38 and HLA-DR), inflammatory monocytes (CD14CD16), T-cell senescence (CD28 and CD57) and exhaustion (PD1), and HDLox, LDLox were assessed at entry and after ART (week 96) with Spearman (partial) correlations.

RESULTS:
HDLox declined and LDLox increased over 96 weeks of ART. Positive associations were observed at baseline and over time between HDLox (but not consistently for LDLox) and most markers of inflammation and immune activation (but not senescence/exhaustion), even after adjustment for multiple comparisons, demographics, entry CD4 cell count and HIV-1 RNA. HDLox was positively associated with IL-6 (r = 0.19 - 0.29, P < 0.01) and sCD163 (r = 0.14 - 0.41, P ≤ 0.04) at all time points.

CONCLUSION:
These prospective longitudinal data suggest that oxidized lipoproteins may contribute to persistent immune activation on ART.

Categories

CRS
Topics

Clinical Trials

P2026: Pharmacokinetic Properties of Antiretroviral and...

IMPAACT P1026s, the predecessor of this study, was first approved in 2003. P1026s enrolled over 1000 pregnant/postpartum women,...

Read More

P1060:  Phase II, parallel, randomized, clinical trials...

A single dose of nevirapine (SD NVP) given to an HIV infected pregnant woman followed by a single dose to her infant has been...

Read More

ACTIV-2/A5401: Adaptive Platform Treatment for Outpatients...

Rationale: There is an urgent need for a platform to rapidly evaluate therapies in the outpatient setting, to prevent disease...

Read More

A5350: Effects of Visbiome Extra Strength on Gut Microbiome...

Many factors contribute to the development of aging-related conditions, including gastrointestinal (GI) diseases, such as...

Read More

A5273: Multicenter Study of Options for Second-Line...

The study is being done with people who are taking their first anti-HIV drug regimen (including an Non-Nucleoside Reverse...

Read More