High-Density Lipoprotein-Mediated Cholesterol Efflux Capacity Is Improved by Treatment With Antiretroviral Therapy in Acute Human Immunodeficiency Virus Infection

Lo, Janet; Rosenberg, Eric S.; Fitzgerald, Michael L.; Bazner, Suzane; Ihenachor, Ezinne J.; Hawxhurst, Victoria; Borkowska, Alison H.; Wei, Jiann-Wu; Zimmerman, Chloe; Burdo, Tricia H.; Williams, Kenneth C.; Freeman, Mason W.; Grinspoon, Steven

doi:10.1093/ofid/ofu108

Cited by 23 publications

(21 citation statements)

References 31 publications

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“…There are limited data regarding the effect of ART on oxidized lipoproteins, lipoprotein particle number and size and HDL function [46]. Contrary to our original hypothesis, raltegravir did not appear to have more favorable effects on HDL ox and %HAE than PI treatment.…”

Section: Discussioncontrasting

confidence: 86%

Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals

Kelesidis

Oda

Borja

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective HDL function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic, treated HIV-1 infection. Design Retrospective study of HDL function measured in two ways in HIV-1 infected males with low overall CVD risk and healthy males with no known CVD risk matched by race to the HIV-1 infected participants. Methods We examined patient level factors associated with two different measures of HDL dysfunction: reduced antioxidant function (oxidized HDL, HDLox) and reduced HDL-apoA-I exchange (HAE), a measure of HDL remodeling, in the HIV infected and control men. Multivariable-adjusted linear regression analyses were employed adjusting for false discovery rate (FDR), age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, albumin. Results In multivariate analysis among HIV-1 infected males (n=166) (median age 45 years, CD4 T cell count 505 cells/mm3, 30.1% were viremic), higher BMI, lower apoA-I and lower albumin were among the most notable correlates of higher HDLox and lower HAE (p<0.05). In HIV-1 uninfected participants lower albumin and higher BMI were associated with lower HAE and higher HDLox, respectively (p≤0.05). HDLox was inversely related to HAE in HIV-1 infected individuals (p<0.001). Conclusion Increased HDLox correlates with reduced HAE in chronic HIV-1 infection. Higher BMI, lower apoA-I and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection using two independent methods.

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Section: Discussioncontrasting

confidence: 86%

Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals

Kelesidis

Oda

Borja

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…This work does provide systematic characterization of lipid particle number, size and CEC longitudinally in HIV-infection following initiation of RAL-based ART, extending previous findings [11,12] that explored the role of ART initiation on these indices.…”

Section: Discussionsupporting

confidence: 72%

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

Funderburg

Playford

et al. 2017

Antiviral Therapy

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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.

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“…3 It is believed that HDL function, rather than serum HDL-C concentrations, may be a more reliable biomarker for CVD risk. 20 In the EPIC-Norfolk study, cholesterol efflux capacity was measured and results supporting the use of cholesterol efflux as an accurate and independent measure to determine the protective effects of HDL. Therefore, development of standardized assays for HDL function measurement seems to be necessary along with HDL-C concentration for clinical applications.…”

Section: Hdl-c Levels Versus Hdl Functionmentioning

confidence: 92%

High‐density lipoprotein functionality and breast cancer: A potential therapeutic target

Samadi

Mobarhan

Mohammadpour

et al. 2018

J of Cellular Biochemistry

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Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high‐density lipoprotein (HDL)‐cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.

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High-Density Lipoprotein-Mediated Cholesterol Efflux Capacity Is Improved by Treatment With Antiretroviral Therapy in Acute Human Immunodeficiency Virus Infection

Cited by 23 publications

References 31 publications

Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals

Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals

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

High‐density lipoprotein functionality and breast cancer: A potential therapeutic target

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