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Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals
Theodoros Kelesidis1, Michael N Oda, Mark S Borja
1*Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA; †Children's Hospital Oakland Research Institute, Oakland, CA; and ‡Department of Medicine Statistics Core, UCLA, Los Angeles, CA.
Insights
High-density lipoprotein (HDL) dysfunction, indicated by increased oxidized HDL (HDLox) and reduced HDL-apoA-I exchange (HAE), is linked to higher BMI, lower apoA-I, and albumin in HIV-1 infected men. These factors contribute to cardiovascular disease risk.
Area of Science:
- Cardiovascular Disease Research
- HIV/AIDS Research
- Lipid Metabolism
Background:
- High-density lipoprotein (HDL) function, not just its level, is crucial for assessing cardiovascular disease (CVD) risk.
- Novel methods allow for the measurement of HDL function using patient samples.
- Understanding HDL dysfunction is key in managing CVD in specific populations like those with HIV-1 infection.
Purpose of the Study:
- To identify factors contributing to HDL dysfunction in chronically treated HIV-1 infected individuals.
- To investigate the relationship between HDL antioxidant function (HDLox) and HDL-apoA-I exchange (HAE) in HIV-1 infection.
- To compare HDL function and associated factors between HIV-1 infected men and healthy controls.
Main Methods:
- A retrospective study design was employed, comparing HDL function in HIV-1 infected men and healthy controls.
- Two measures of HDL dysfunction were assessed: reduced antioxidant function (HDLox) and reduced HDL-apoA-I exchange (HAE).
- Multivariable-adjusted linear regression analyses were performed, controlling for various clinical and demographic factors.
Main Results:
- In HIV-1 infected men, higher body mass index (BMI), lower apolipoprotein A-I (apoA-I), and lower albumin were significantly associated with higher HDLox and lower HAE.
- Similar associations were observed in HIV-1 uninfected participants, with lower albumin linked to lower HAE and higher BMI to higher HDLox.
- A significant inverse relationship was found between HDLox and HAE in HIV-1 infected individuals, indicating a correlation between impaired antioxidant function and remodeling.
Conclusions:
- HDL dysfunction, characterized by increased HDLox and reduced HAE, is prevalent in chronic HIV-1 infection.
- Higher BMI, lower apoA-I, and lower albumin are key factors associated with HDL dysfunction in this population.
- These findings highlight potential therapeutic targets for mitigating CVD risk in individuals with HIV-1 infection.
Objective:
High-density lipoprotein (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 2 ways in HIV-1-infected men with low overall CVD risk and healthy men with no known CVD risk matched by race to the HIV-1-infected participants.
Methods:
We examined patient-level factors associated with 2 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 used adjusting for false discovery rate, age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, and albumin.
Results:
In multivariate analysis among HIV-1-infected men (n = 166) (median age 45 years, CD4 T-cell count 505 cells/mm, 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).
Conclusions:
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 2 independent methods.
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