Sydney, Australia - At least eight years of highly active antiretroviral therapy (HAART) does not appear to be associated with an increased risk for subclinical atherosclerosis as measured by coronary artery calcium (CAC) deposits, according to the findings of a new analysis [1].

Dr Lawrence A Kingsley (University of Pittsburgh, PA) presented the findings here at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.

The findings are in contrast to the results of several trials suggesting that HAART use is linked to metabolic changes that may increase the risk for coronary atherosclerosis in HIV+ patients. However, Kingsley said that many studies have focused on the risk for MI and other "hard" cardiovascular end points relative to HAART usage, "particularly with respect to protease-inhibitor use."

"Our study focused on subclinical coronary atherosclerosis and found lower levels of coronary calcium by computed tomography examination among the long-term HAART users relative to age-matched and other cardiovascular-risk-factor-matched, HIV-negative controls," Kingsley said.

According to Kingsley, the current study is the first relatively large study to evaluate this issue.

The study included 947 men, of whom 332 tested negative for HIV, 84 HIV+ patients who had not received treatment, and 531 previously treated HIV+ patients. All patients were older than 40 years.

Each participant underwent two CT scans designed to measure the presence of CAC. Increasing age was the risk factor associated most strongly with calcium deposits, regardless of HIV infection or treatment status.

After adjusting for age, researchers found that neither long-term HAART use (OR 1.5, 95% CI 1.04-2.25) nor HIV infection itself (OR 1.4, 95% CI 0.81-2.50) was associated with an increased likelihood of calcium in the coronary arteries.

Moreover, patients taking HAART had a lower calcium score compared with uninfected controls; for HAART use of one to seven years, the relative CAC extent was 0.74 (95% CI 0.52-1.05), and for HAART use of more than eight years, it was 0.68 (95% CI 0.49-0.95). However, when the researchers accounted for traditional coronary risk factors, they found that HAART had no significant effect on CAC levels.

"I would argue against using these preliminary data to support changes in clinical practice until we can fully understand the meaning of lower coronary artery calcium levels in long-term HAART users," Kingsley pointed out. "Many unanswered questions remain, including the need to explain why coronary calcium levels were lower among long-term HAART users and what the mechanism for that might be.

"It would also be interesting to note whether rate of progression of coronary calcium is decreased among HIV-infected men taking lipid-lowering medications," he added.

"These findings underscore how incomplete our knowledge is regarding the long-term cardiovascular effects of antiretroviral therapy," meeting attendee Dr Paul Sax (Brigham and Women's Hospital, Boston, MA) commented.

"While antivirals induce dyslipidemia and insulin resistance, on the other side of the risk equation, we also know from the [Strategies for Management of Antiretroviral Therapy] SMART study that interrupting therapy may actually increase the risk of cardiovascular events," he said. "The rate of these events also increases in patients with lower CD4+ cell counts," he added.

According to Sax, coronary artery calcification is a reliable surrogate for cardiovascular risk. "We will have to add the results of this study to the sometimes-conflicting data we have in this area already—I agree with Dr Kingsley that it is premature to use these results to alter clinical practice," Sax added.