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Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses

Hsue, Priscilla Ya; Hunt, Peter Wb; Sinclair, Elizabethc; Bredt, Barryc; Franklin, Arlanaa; Killian, Maudic; Hoh, Rebeccab; Martin, Jeffrey Nb,d; McCune, Joseph Mc; Waters, David Da; Deeks, Steven Gb

doi: 10.1097/QAD.0b013e3280108704
Basic Science

Objectives: HIV-infected subjects are at increased risk for myocardial infarction. The mechanism of this increased risk remains unclear. Since cytomegalovirus (CMV) infection has been associated with accelerated atherosclerosis in the transplant population and immune responses against CMV may be altered by HIV disease, we hypothesized that enhanced T-cell responses against CMV would be associated with increased atherosclerosis in subjects with HIV.

Methods: We measured high-sensitivity C-reactive protein (hs-CRP), T-cell activation, CMV-specific T-cell responses, and carotid artery intima-media thickness (IMT) in 93 HIV-infected subjects and in 37 uninfected controls.

Results: The mean age of the HIV-infected subjects was 48 years and 85 (91%) were male. The median carotid IMT was higher in the HIV-infected group compared to the uninfected group (0.95 mm versus 0.68 mm, P < 0.001). This difference remained significant after controlling for all traditional risk factors. Compared to HIV-negative controls, HIV-infected subjects had higher median levels of hs-CRP (P = 0.05), higher levels of CD4 and CD8 T-cell activation (P < 0.0001) and higher CMV-specific interferon-γ CD8 T-cell responses (P < 0.0001). CMV-specific T-cell responses, but not hs-CRP and T-cell activation, were independently associated with higher carotid IMT (P = 0.001).

Conclusions: HIV-infected subjects had thicker carotid IMT compared to controls. While HIV patients also had higher T-cell activation, hs-CRP levels, and CMV-specific T-cell responses, only CMV-specific T-cell responses were independently associated with IMT. Accelerated atherosclerosis in HIV patients may be mediated by heightened CMV-induced immune responses.

From the aDivisions of Cardiology, USA

bPositive Health Program, USA

cGeneral Clinical Research Centre, San Francisco General Hospital, University of California, San Francisco, USA

dDivision of Experimental Medicine, Department of Medicine, USA

eDepartment of Epidemiology and Biostatistics, University of California, San Francisco, USA.

Received 2 June, 2006

Revised 16 August, 2006

Accepted 5 September, 2006

Correspondence to Priscilla Y. Hsue, Room 5G1, Division of Cardiology, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA. Tel: +1 415 206 8257; fax: +1 415 206 5100; e-mail: phsue@medsfgh.ucsf.edu

Presented in part at the 13th Conference on Retroviruses and Opportunistic Infections. Denver, CO, February 5–8, 2006 [abstract 741].

© 2006 Lippincott Williams & Wilkins, Inc.