HIV infection induces structural and functional changes in high density lipoproteins.
OBJECTIVE
Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients.


RESULTS
Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/μl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/μl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/μl, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/μl, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/μl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R(2) = 0.2611, p < 0.05; R(2) = 0.2722, p < 0.05; and R(2) = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R(2) = 0.26, p = 0.026).


CONCLUSIONS
Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population.
Division of Infectious Diseases, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Marc O
MO
Siegel
Lipid Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alison G
AG
Borkowska
Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Larisa
L
Dubrovsky
Kansas Lipidomics Research Center, Kansas State University, Manhattan, KS, USA.
Mary
M
Roth
Kansas Lipidomics Research Center, Kansas State University, Manhattan, KS, USA.
Ruth
R
Welti
Division of Infectious Diseases, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Afsoon D
AD
Roberts
Division of Infectious Diseases, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
David M
DM
Parenti
Division of Infectious Diseases, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Gary L
GL
Simon
Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
Dmitri
D
Sviridov
Department of Epidemiology and Biostatistics, George Washington University, Milken Institute School of Public Health, Washington, DC, USA.
Samuel
S
Simmens
Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. Electronic address: mbukrins@gwu.edu.
Michael
M
Bukrinsky
Lipid Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: mfitzgerald@ccib.mgh.harvard.edu.
Michael L
ML
Fitzgerald
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D040901:Proteomics; D019562:Viral Load
D019380:Anti-HIV Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010718:Phosphatidylserines; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C113656:PON3 protein, human; D010100:Oxygen
Anti-retroviral treatment; Atherosclerosis; Cholesterol efflux; HDL; HIV; Lipidomics; PON; Proteomics