Traditional risk factors for heart disease, not treatment with a protease inhibitor, are associated with hardening of the carotid artery, according to a US study published in the June 10th edition of AIDS. This finding is in contrast to some earlier studies, but the investigators stress the strength of their study, particularly their matching of HIV-positive patients taking a protease inhibitor with HIV-positive patients not on protease inhibitor therapy and HIV-negative controls according to traditional risk factors for cardiovascular disease.
“There is an urgent need to determine whether people with HIV infection are at an increased risk for atherosclerosis”, note the investigators. Several factors have been associated with an increased risk of cardiovascular disease in HIV-positive individuals, including chronic inflammation due to HIV, metabolic abnormalities caused by protease inhibitors, and “the intersection of traditional risk factors (smoking status, blood pressure, age, sex, race and menopausal status) with HIV-specific factors”, comment the researchers.
Accordingly, investigators designed a prospective study to identify the role of protease inhibitors in the development of subclinical hardening of the arteries. The objective was to compare carotid intima-media thickness (IMT) between HIV-infected individuals taking a protease inhibitor, HIV-positive patients not on protease inhibitor therapy and HIV-negative controls.
The investigators write, “a unique feature of the study design was the enrollment of subjects…into a triad consisting of an individual from each group.” Each individual in a triad was matched on six cardiovascular disease risk factors: age, sex, race, blood pressure status (normal or hypertensive), smoking status and menopausal status.
Carotid artery IMT was measured using a high-resolution ultrasound.
A total of 134 individuals were recruited to the study and divided into 45 triads. Individuals had a median age of 42 years, and the overwhelming majority were male (40 triads) and white (76%, 34 triads).
Median IMT was 0.69mm in HIV-positive individuals taking protease inhibitors, 0.71mm in HIV-positive patients not taking a protease inhibitor and 0.69mm in HIV-negative controls. “Since there was no statistically significant difference between group 1 and group 2, it was concluded that there was no evidence of a protease inhibitor therapy effect on carotid IMT”, note the investigators. The two groups of HIV-positive patients were then compared to the HIV-negative controls and the investigators found that there was no statistically significant difference in IMT thickness between HIV-infected and HIV-negative individuals.
The investigators then examined all the study members’ cardiovascular risk factors. Univariate analysis indicated that IMT thickness increased with age (p = 0.002), body mass index (p = 0.002), waist circumference (p = 0.01), and was increased in non-Hispanic whites (p = 0.48), but tended to be lower in women (p = 0.05) and in individuals with increased high-density lipoprotein (HDL) cholesterol (p = 0.02).
In multivariate analysis increased IMT thickness was predicted by age (p = 0.002) and body mass index (p = 0.012). Increased HDL cholesterol was protective against increases in IMT.
“There is no evidence from the carotid IMT data of this study to support an atherogenic effect of HIV status or protease inhibitor therapy, after a median duration of protease inhibitor exposure of 216 weeks”, comment the investigators.
The investigators note that their findings are in variance at those of other studies. They concede that that this could be because they excluded individuals with a family history of heart disease and uncontrolled hypertension. They speculate “the effect of protease inhibitor-based HAART on the development of atherosclerosis first becomes evident in patients who are already pre-disposed to disease on the basis of other risk factors.”
However, they emphasise the careful design of their study, which was the first to control for traditional risk factors prospectively. “There was no relationship detected between HIV infection or protease inhibitor therapy and a static measure of carotid IMT”, they conclude.
Currier JS et al. Carotid artery intima-media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure. AIDS 19: 927 – 933, 2005.