Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: further evidence for a unique form of metabolic syndrome in HIV patients

Metabolism. 2013 Jul;62(7):1014-20. doi: 10.1016/j.metabol.2013.01.020. Epub 2013 Mar 19.

Abstract

Introduction: Plasma triglycerides (TG) and HDL-C are inversely related in Metabolic Syndrome (MetS), due to exchange of VLDL-TG for HDL-cholesteryl esters catalyzed by cholesteryl ester transfer protein (CETP). We investigated the relationship of TG to HDL-C in highly-active antiretroviral drug (HAART)-treated HIV patients.

Methods: Fasting plasma TG and HDL-C levels were compared in 179 hypertriglyceridemic HIV/HAART patients and 71 HIV-negative persons (31 normotriglyceridemic (NL) and 40 hypertriglyceridemic due to type IV hyperlipidemia (HTG)). CETP mass and activity were compared in 19 NL and 87 HIV/HAART subjects.

Results: Among the three groups, a plot of HDL-C vs. TG gave similar slopes but significantly different y-intercepts (9.24±0.45, 8.16±0.54, 6.70±0.65, sqrt(HDL-C) for NL, HIV and HTG respectively; P<0.001); this difference persisted after adjusting HDL-C for TG, age, BMI, gender, glucose, CD4 count, viral load and HAART strata (7.18±0.20, 6.20±0.05 and 4.55±0.15 sqrt(HDL-C) for NL, HIV and HTG, respectively, P<0.001). CETP activity was not different between NL and HIV, but CETP mass was significantly higher in HIV (1.47±0.53 compared to 0.93±0.27μg/mL, P<0.0001), hence CETP specific activity was lower in HIV (22.67±13.46 compared to 28.46±8.24nmol/μg/h, P=0.001).

Conclusions: Dyslipidemic HIV/HAART patients have a distinctive HDL-C plasma concentration adjusted for TG. The weak inverse relationship between HDL-C and TG is not explained by altered total CETP activity; it could result from a non-CETP-dependent mechanism or a decrease in CETP function due to inhibitors of CETP activity in HIV patients' plasma.

Trial registration: ClinicalTrials.gov NCT00246376.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Biomarkers / blood
  • Body Mass Index
  • CD4 Lymphocyte Count
  • Cholesterol Ester Transfer Proteins / blood*
  • Cholesterol Ester Transfer Proteins / metabolism
  • Cholesterol, HDL / blood*
  • Cohort Studies
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV-Associated Lipodystrophy Syndrome / blood*
  • HIV-Associated Lipodystrophy Syndrome / complications
  • HIV-Associated Lipodystrophy Syndrome / virology
  • Humans
  • Hyperlipoproteinemia Type IV / blood
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / virology
  • Middle Aged
  • Overweight / complications
  • Triglycerides / blood*

Substances

  • Biomarkers
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Triglycerides

Associated data

  • ClinicalTrials.gov/NCT00246376