Low CD4 cell count, but not HIV treatment, increases risk of hardening of the arteries

HIV-positive patients with a low CD4 cell count have an increased risk of vascular disease, a US study published in the August 20^th edition of AIDS reports. Unlike some earlier research, however, the study found little evidence that HIV treatment increased the risk of vascular disease, although men who received protease inhibitors did have a slightly elevated risk of lesions in the carotid artery.

The authors of an editorial which accompanies the study stress the importance of a low CD4 cell count as a risk factor for cardiovascular disease and conclude “treatment of HIV disease with restoration of immunity is good for the heart”.

A number of recent studies have linked HIV treatment with an increased risk of cardiovascular disease and subclinical atherosclerosis – hardening of the arteries that is not causing illness. There is other evidence, most notably the SMART treatment interruption study, suggesting that HIV-positive patients with a low CD4 cell count have an increased risk of cardiovascular illness. But other studies have produced contradictory findings, both about the association between HIV treatment and heart disease, and regarding the link between CD4 cell count and cardiovascular disease.

Investigators therefore designed a study to look at the association between infection with HIV, markers of the severity of HIV disease (CD4 cell count, viral load and progression to AIDS) and the use of antiretroviral drugs and subclinical vascular disease.

The study was prospective and included individuals drawn from two large and well-established research cohorts, one of which involved women (the Women’s Interagency HIV Study [WIHS]), the other men (Multicenter AIDS Cohort [MACS]). The composition of these study populations allowed the investigators to judge the effect of both HIV infection and the use of anti-HIV drugs on the risk of vascular disease as they both include HIV-positive individuals not on antiretroviral therapy, HIV-positive individuals receiving HIV treatment, and HIV-negative individuals.

Subclinical hardening of the arteries was assessed using an ultrasound examination of the carotid artery. The investigators checked for evidence of hardening, or thickening of the arteries, and for arterial lesions. Recruitment to the study started in April 2004 and the total population included 1865 women (1331 of whom were HIV-positive), and 935 men (of whom 600 were HIV-positive).

There were no significant differences in arterial thickness between HIV-positive and HIV-negative women, nor between HIV-positive and HIV-negative men. Nor did the investigators find any association overall between infection with HIV and the presence of lesions in the carotid artery.

But when they looked at their results in more detail, they found that, in HIV-positive individuals with a CD4 cell count below 200 cells/mm³, the prevalence of carotid lesions was increased 70% in women (p = 0.05) and 93% in men (p = 0.02) compared to HIV-negative individuals.

The investigators then considered antiretroviral treatment as a risk factor for carotid lesions. Their first set of analyses showed that longer duration of treatment with a protease inhibitor increased the risk of carotid lesions in men (p = 0.05), but when they took into consideration other risk factors, this association ceased to be statistically significant. No association was found between treatment with a protease inhibitor and carotid lesions in women, nor was there any association between the use of NRTI and NNRTI drugs and the carotid lesions.

Unsurprisingly, the investigators found that in both HIV-positive women and men, hardening of the carotid artery was associated with traditional risk factors for cardiovascular disease such as increasing age, smoking, diabetes, higher body mass index, and cholesterol levels. If HIV-positive individuals had lesions in their carotid artery, they were also significantly more likely to have evidence of hardening of the carotid artery (p

The investigators believe that the lack of clear and consistent findings of an association between antiretroviral therapy and hardening of the carotid artery “is evidence against the hypothesis that antiretroviral medications are an important cause of vascular disease.”

They also emphasise the finding that a low CD4 cell count was associated with evidence of vascular disease and conclude that “the association of antiretroviral therapy use and other HIV-related variables with atherosclerosis needs to be studied further.”