Human immunodeficiency virus per se exerts atherogenic effects



      Premature atherosclerosis in HIV-infected patients has been attributed to highly active antiretroviral therapy (HAART) and the associated metabolic complications. Whether HIV per se plays a role is an unresolved issue. The purpose of this study was to evaluate whether HIV per se exerts atherogenic effects.


      We measured carotid intima–media thickness (IMT) and brachial endothelial-dependent (FMD) and endothelial-independent (NMD) vasodilation in 38 naïve untreated HIV-infected patients and 41 healthy control subjects.


      Control subjects were selected as to match the HIV patients for metabolic risk factors. Mean carotid IMT was higher in HIV patients (0.85 ± 0.2 mm; p < 0.001) than in controls (0.63 ± 0.1 mm). In a stepwise multiple regression model, the changes in carotid IMT were predicted by the duration of HIV infection (p < 0.001) and CD4 T-cells (p = 0.035). Brachial FMD was impaired in HIV patients (8.8 ± 3% versus 12.2 ± 3% in controls; p < 0.001). In contrast, NMD values practically overlapped in the HIV patients and controls. Analysis of the data in relation to viral load showed that FMD was significantly more impaired in the subgroup of patients with viral load values above the median (p < 0.001). In addition, there was a highly significant, inverse correlation between FMD and the HIV-RNA copies (p < 0.001).


      HIV infection causes functional and structural vascular alterations in a very early stage of the infection independent of HAART and metabolic factors. The data lend support to the viral infectious theory of atherosclerosis. Early assessment of the vascular status in HIV-infected patients is suggested.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Palella Jr., F.J.
        • Delaney K.M.
        • Moorman A.C.
        • et al.
        Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.
        N Engl J Med. 1998; 338: 853-860
        • Holmberg S.D.
        • Moorman A.C.
        • Williamson J.M.
        • et al.
        Protease inhibitors and cardiovascular outcomes in patients with HIV-1.
        Lancet. 2002; 360: 1747-1748
        • Schneider M.F.
        • Gange S.J.
        • Williams C.M.
        • et al.
        Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984–2004.
        AIDS. 2005; 18: 2009-2018
        • Bozzette S.A.
        • Ake C.F.
        • Tam H.K.
        • Chang S.W.
        • Louis T.A.
        Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection.
        N Engl J Med. 2003; 348: 702-710
        • Friis-Moller N.
        • Sabin C.A.
        • Weber R.
        • et al.
        Combination antiretroviral therapy and the risk of myocardial infarction.
        N Engl J Med. 2003; 349: 1993-2003
        • d’Arminio A.
        • Sabin C.A.
        • Phillips A.N.
        • et al.
        Cardio- and cerebrovascular events in HIV-infected persons.
        AIDS. 2004; 18: 1811-1817
        • van Wijk J.P.
        • de Koning E.J.
        • Cabezas M.C.
        • et al.
        Functional and structural markers of atherosclerosis in human immunodeficiency virus-infected patients.
        J Am Coll Cardiol. 2006; 47: 1117-1123
        • Dhawan S.
        • Puri R.K.
        • Kumar A.
        • et al.
        Human immunodeficiency virus-1-tat protein induces the cell surface expression of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in human endothelial cells.
        Blood. 1997; 90: 1535-1544
        • Park I.W.
        • Ullrich C.K.
        • Schoenberger E.
        • Ganju R.K.
        • Groopman J.E.
        HIV-1 Tat induces microvascular endothelial apoptosis trough caspase activation.
        J Immunol. 2001; 167: 2766-2771
        • Oliviero U.
        • Orefice G.
        • Coppola G.
        • et al.
        Carotid atherosclerosis and ischemic stroke in young patients.
        Int Angiol. 2002; 21: 117-122
        • De Groot E.
        • Hovingh K.
        • Wiegman A.
        • et al.
        Measurement of arterial wall thickness as a surrogate marker for atherosclerosis.
        Circulation. 2004; 109: 33-38
        • Corretti M.C.
        • Anderson T.J.
        • Benjamin E.J.
        • et al.
        Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the international brachial artery reactivity task force.
        J Am Coll Cardiol. 2002; 39: 257-265
        • Stein J.H.
        • Klein M.A.
        • Bellehumeur J.L.
        • et al.
        Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction.
        Circulation. 2001; 104: 257-262
        • Hsue P.Y.
        • Lo J.C.
        • Franklin A.
        • et al.
        Progression of atherosclerosis as assessed by carotid intima–media thickness in patients with HIV infection.
        Circulation. 2004; 109: 1603-1608
        • Blum A.
        • Hadas V.
        • Burke M.
        • Yust I.
        • Kessler A.
        Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction.
        Clin Cardiol. 2005; 28: 149-153
        • Charakida M.
        • Donald A.E.
        • Green H.
        • et al.
        Early structural and functional changes of the vasculature in HIV-infected children.
        Circulation. 2005; 112: 103-109