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Increased Carotid Intima-media Thickness in HIV-infected Patients Is Associated with Increased C-reactive Protein Levels and Increased Cytomegalovirus Specific T Cell Activation
Priscilla Hsue*1,2, P Hunt1,2, D Waters1,2, E Sinclair3, J Martin1,2, A Franklin2, R Hoh1,2, and S Deeks1,2
1Univ of California, San Francisco, US; 2San Francisco Gen Hosp Med Ctr, CA, US; and 3Gladstone Inst of Virology and Immunology, Univ of California, San Francisco, US
Background: HIV patients are at increased risk for
myocardial infarction. However, the mechanism accounting for this increased
risk remains unclear. Since cytomegalovirus (CMV) infection has been associated
with accelerated atherosclerosis in the heart transplant population and
CMV-specific immunity is altered by HIV disease, we hypothesized that CMV would
be associated with increased atherosclerosis in HIV patients.
Methods: We measured high
sensitivity C-reactive protein (hs-CRP), T cell
activation, and carotid artery intima-media thickness (IMT) by ultrasound in 93
HIV-infected patients and in 37 uninfected controls. HIV-infected subjects were
required to be on a stable ART regimen or no ART for 1 year. CMV-specific
immune responses were defined as the proportion of CD4+ and CD8+
T cells which produced interferon-gamma in response to CMV pp65 protein. T cell
activation was based on the mean density of CD38 on T cell subsets.
Results: The median age of
the HIV-infected patients was 46 years and 75 (81%) were male. The median CD4
count was 354 cells/mm3, and 57% of patients had a viral load <75
copies/ml. Most patients (92%) were on antiretroviral treatment. Compared to
HIV-negative controls, HIV-infected subjects had higher median baseline carotid
IMT (0.95 mm vs 0.68 mm, p <0.001). This difference remained significant after
controlling for all traditional risk factors. Compared to controls,
HIV-infected patients had higher median levels of hs-CRP (1.1 mg/L vs 0.8 mg/L, p = 0.05),
higher levels of T cell activation (745 vs 282 CD38
molecules/CD8+ T cell, P <0.0001),
and higher CMV-specific T cell responses (2.09% vs
0.056% CMV-specific CD8+ T cells, p <0.0001). hs-CRP levels and CMV-specific T cell responses, but not T
cell activation were independently associated with higher carotid IMT. Although
HIV infection was independently associated with carotid IMT after adjustment
for CRP (p <0.001), this effect
was no longer significant after adjustment for CMV-specific T cell responses (p = 0.11).
Conclusions: HIV-infected subjects had thicker carotid IMT
as compared to HIV-negative controls. Their hs-CRP levels and CMV-specific T
cells responses were also higher, and both of these measures were independently
associated with carotid IMT. HIV infection may accelerate atherosclerosis
through CMV-induced immune responses and/or inflammation.
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