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

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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.



Relating to the heart and blood vessels.

traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.


A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 


A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

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.


Friis-Moller N et al. Exposure to HAART is associated with an increased risk of myocardial infarction: The DAD study. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003, abstract 130.

Currier J et al. Carotid intima-media thickness in HIV-infected and uninfected adults: ACTG 5078. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003, abstract 131.

Hsue P et al. Increased atherosclerotic progression in patients with HIV: The role of traditional and immunological risk factors. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003, abstract 139lb.