Cardiovascular risks of HAART: More data but little more clarity?

Boston, MA: At last year’s Retroviruses Meeting in Seattle, conflicting reports on the rate of cardiovascular disease amongst people taking HAART proved to be an enduring controversy in HIV medicine. This year in Boston, this issue continues to provoke disagreement.

Further data from the landmark DAD trial, an observational study involving eleven HIV patient cohorts and covering three continents, were reported yesterday. Established to track long-term antiretroviral safety, DAD investigators presented an analysis of the frequency of heart attacks (myocardial infarctions, or MI) in people exposed to HAART. During over 36,000 patient years of follow-up, 126 people developed an MI, 36 of which were fatal. The incidence of MI increased with additional years on combination antiretroviral therapy, resulting in a 26% increased risk of MI per year of drug exposure.

Traditional risk factors such as gender, age, smoking, raised cholesterol and diabetes were observed to predict risk of MI. And overall, the frequency of reported MI remained low at 3.5 cases per 1,000 patient years of follow-up.

The carotid artery, which is found in the neck and carries blood to the brain, has been an object of particular interest for Boston delegates this week. Measuring the depth of the walls of this artery (known as the intima media thickness, or IMT) is a commonly used surrogate marker for coronary atherosclerosis, a ‘furring’ of the arteries which increases risk of heart attack.

Two US groups presented conflicting data on progression of carotid IMT in people with HIV. Judith Currier reported from ACTG 5078, a matched case control study assessing carotid IMT in HIV-positive people on protease inhibitors (PIs) for more than two years, compared to HIV-positive people who had not received PIs, and to HIV-negative people. This study excluded people with a family history of cardiovascular disease, or with diabetes, or who had a viral load above 10,000 copies, as these factors made matching difficult. Taking just one measure of carotid IMT, Currier’s group found no differences at baseline between the three arms.

In a late breaking presentation, Hsue and colleagues reported on carotid IMT in 106 HIV-positive adults, and compared these with data from histroical controls. IMT was derived by calculating the mean of twelve intima medial segments measured, As with Currier’s study, Hsue found that increased IMT was associated with traditional cardiovascular risk factors such as age, LDL cholesterol, hypertension, and smoking. In mutlivariate analysis, Hsue observed that having a nadir CD4 count below 200 was a further predictor of risk.

Carotid IMT was increased at baseline compared to large studies performed in HIV-negative populations. Further, Hsue calculated the rate of IMT progression based on data from the first 22 consecutive patients returning for follow-up. The median rate of IMT progression was 0.1 mm/year, and progression was predicted by age and duration of PI use. This rate appears to compare poorly with reported progression rates in HIV-negative populations of less than 0.04mm/year.