icon-    folder.gif   Conference Reports for NATAP  
  17th CROI
Conference on Retroviruses
and Opportunistic Infections
San Francisco CA
February 16-19, 2010
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Inflammation Tied to Endothelial Dysfunction Despite Tight HIV Control
Mark Mascolini
People taking effective antiretroviral regimens--even those not including a protease inhibitor (PI) or abacavir--had lower endothelial flow-mediated vasodilation than HIV-negative people [1]. In the HIV group, high-sensitivity C-reactive protein (hsCRP), an inflammation marker, correlated with impaired flow-mediated dilation, whereas older age correlated more closely with impaired dilation in a comparison group of people without HIV. Endothelial dysfunction is a key mechanism in atherosclerosis and a marker of heart disease.
This study compared 139 HIV-infected people in the SCOPE cohort at San Francisco General Hospital with 34 HIV-negative controls. The HIV group had been taking antiretrovirals for at least 24 months and had not changed drugs for at least 12 months. They all had a viral load below 75 copies on their two most recent assays. In the 12 weeks before the study, they could add no new antihypertensive or lipid-lowering drug or change a dose of those drugs.
The HIV group was significantly older than the 34 HIV-negative controls (median 51 versus 38 years, P < 0.001). Nine people in the HIV group and no controls had a history of coronary artery disease, a difference that stopped short of statistical significance (P = 0.07). Forty people with HIV had hypertension, compared with 2 controls (P < 0.0001). Equivalent proportions of the two groups smoked (51% and 56%) or had diabetes (4% and 0).
People with HIV had been infected for a median of 17 years and had taken antiretrovirals for 8.9 years. Median PI duration was 7.4 years, and 40 people were taking abacavir at the time of the study. Current median CD4 count stood at 310 and nadir (lowest-ever) count at 96.
Priscilla Hsue and colleagues assessed endothelial function as flow-mediated vasodilation of the brachial artery. Technicians blinded to each person's HIV and treatment status analyzed the images. The researchers also measured hsCRP as a marker of inflammation.
Flow-mediated vasodilation was significantly lower (worse) in the HIV group (4.1% versus 5.2%, P = 0.017). The difference remained significant after statistical adjustment for traditional cardiovascular risk factors.
HIV-infected people had a significantly higher median hsCRP than controls, and hsCRP was independently associated with HIV infection after adjustment for risk factors (P = 0.035). Higher hsCRP also correlated with worse flow-mediated vasodilation (rho = -0.21, P = 0.03) in people with HIV. In contrast, age correlated with worse vasodilation in the uninfected group (rho = -0.48, P = 0.004).
Current abacavir use, but not PI use, was also associated with impaired flow-mediated vasodilation after adjustment for other risk factors, including glomerular filtration rate (P = 0.043). However, compared with the HIV-negative group, even people taking regimens that did not include PIs or abacavir had lower flow-mediated vasodilation. Duration of antiretroviral therapy, nadir CD4 count, and latest CD4 count did not correlate with dilation.
Hsue and coworkers believe their findings "suggest that even patients doing well on combination antiretroviral therapy (as defined by viral load) may be at increased risk for cardiovascular disease, and that chronic inflammation in the setting of treated HIV disease likely contributes to this increased risk."
The investigators also suggest their results "argue for an independent role of direct drug toxicity in driving early cardiovascular disease" in people with HIV.
1. Hsue P, Hunt P, Schnell A, et al. Inflammation is associated with endothelial dysfunction among individuals with treated and suppressed HIV infection. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 708.