Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses.
OBJECTIVE
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-gamma 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.
Hsue
Priscilla Y
PY
Divisions of Cardiology, San Francisco General Hospital, University of California, San Francisco, USA. phsue@medsfgh.ucsf.edu
Hunt
Peter W
PW
Sinclair
Elizabeth
E
Bredt
Barry
B
Franklin
Arlana
A
Killian
Maudi
M
Hoh
Rebecca
R
Martin
Jeffrey N
JN
McCune
Joseph M
JM
Waters
David D
DD
Deeks
Steven G
SG
D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002339:Carotid Arteries / Q000473:pathology*; D003430:Cross-Sectional Studies; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D017539:Tunica Intima / Q000473:pathology*
D000914:Antibodies, Viral; D007371:Interferon-gamma; D002097:C-Reactive Protein