Background:  Cardiovascular disease (CVD) and acute vascular events often occur in HIV-1-infected adults younger than 50 years of age, suggesting an accelerated rate of atherosclerosis in this population. The mechanisms responsible for the heightened cardiovascular risk in individuals infected with HIV-1 under the age of 50 years are not clear. Impairments in vascular endothelial function, particularly endothelium-dependent vasodilation, play an important role in the pathogenesis of CVD and increase with advancing age. The aim of this study was to determine whether endothelium-dependent vasodilation is impaired in untreated HIV-1-seropositive men compared with healthy men of similar age and, if so, whether the degree of impairment in untreated HIV-1 seropositive men is similar to that of older healthy men.

Methods:  To address this aim we studied:  10 healthy young (age 36±3 years), 10 healthy older (62±1 year) men and 10 young HIV-1-seropositive treatment-naive (34±2 years) men. All subjects were non-obese and free of overt cardiometabolic disease. Forearm blood flow (FBF) responses to intrabrachial infusions of acetylcholine (an endothelium-dependent vasodilator; ACh; 8.0 to 32.0 µg/min) and sodium nitroprusside (an endothelium-independent vasodilator) (2.0 to 8.0 µg/min) were measured by venous occlusion plethysmography. Group differences in FBF responses to each vasoactive agent were determined by repeated measures ANOVA.

Results:  FBF responses to ACh were ~25% lower (p <0.01) in the HIV-1-seropositive (from 4.4±0.3 to 13.5±1.2 mL/100 mL tissue/min) compared with healthy (5.0±0.4 to 17.8±0.9 mL/100 mL tissue/min) men of similar age. Of note, the FBF responses to ACh between the HIV-1-seropositive men and healthy older (4.9±0.3 to 13.1±0.9 mL/100 mL tissue/min) men were not different (p = 0.89). There were no significant differences amongst the groups in FBF responses to sodium nitroprusside, indicating that the observed differences in ACh-mediated vasodilation between the young healthy and untreated HIV-1-seropositive men were endothelium-dependent.

Conclusions:  Endothelium-dependent vasodilation in young untreated HIV-1-infected men is markedly lower than their healthy peers and similar to that of healthy men 25 years older. These data indicate that untreated HIV-1 infection is associated with accelerated vascular aging. Impaired endothelial function may contribute to the increased risk of vascular events in HIV-1-seropositive adults under the age of 50 years.