7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13–16 November 2005, Dublin, Ireland

HIV-1 infection diverts reverse cholesterol transport toward atherogenic pathway

H Rose¹, J Hoy², I Woolley², A Dart¹ and D Sviridov^1
1Baker Heart Research Institute, Melbourne, Victoria, Australia; ²Department of Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia

Antiviral Therapy 2005; Supplement 3:L14 (abstract no. 21)

BACKGROUND: HIV infection and its treatment with protease inhibitors (PI) is associated with an atherogenic lipid profile including hypoalphalipoproteinaemia, yet no study has investigated the impact of HIV on specifically reverse cholesterol transport (RCT). RCT is a pathway that acts to remove excessive cholesterol from macrophages in the arterial wall to the plasma high density lipoprotein (HDL), thus protecting against development of atherosclerosis. HDL is then re-modelled through esterification of its cholesterol, by lecithin cholesterol acyl-transferase (LCAT), and by exchanging cholesteryl esters and phospholipids with other lipoproteins through the action of cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP). The proportion of cholesterol delivered to the liver for excretion or to the atherogenic lipoproteins may determine the protective efficiency of RCT.

METHODS: A 20 ml blood sample was taken from male volunteers; 33 HIV-negative controls, 25 HIV-positive untreated patients and 28 HIV-positive PI-treated patients. Lipids, lipoproteins and RCT transfer protein’s mass and activities were measured. Viral load, CD4+ cell count and CD4 % were also measured for subjects in the HIV groups.

RESULTS: Plasma triglyceride level, mass and activity of LCAT and CETP activity were all significantly higher in both HIV groups compared with the control (P<0.05). Plasma HDL-C and preb₁-HDL levels were significantly lower in both HIV groups (P<0.05), whereas plasma apolipoprotein A-I (apoA-I) levels were unchanged. There was a significant positive correlation between apoA-I and CD4+ cell levels in the combined HIV data (r=0.5, P<0.01). There was no difference between treated and untreated HIV patients in all but one of the RCT parameters. The only parameter affected by treatment was a significantly lower activity of PLTP (P<0.05).

CONCLUSIONS: Reverse cholesterol transport in HIV patients is diverted toward transferring cholesterol from anti-atherogenic HDL toward atherogenic apolipoprotein- B-containing lipoproteins. This would reduce the efficiency of RCT and consequently increase the risk of development of atherosclerosis. Our findings also suggest that CETP inhibitors may be effective for correcting the effect of HIV on RCT. Furthermore, our findings suggest that HIV infection itself, rather than treatment is likely to be the major contributor to the impairment of RCT in HIV patients.

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2005-11-13
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