Nov. 19, 2003 -- There's little doubt that AIDS "cocktails" have led to increased survival for HIV-infected people. But a major new study shows these drugs may increase the risk of heart attack, even in relatively young survivors.
A multinational team of researchers estimate that for each year patients take this combination drug therapy, their risk of heart attack increases 26% -- at least during their initial four to six years of treatment.
Still, when the researchers took into account other risk factors associated with heart disease, they found the actual rate of heart attacks from these drugs alone was quite low. Among all the patients that died during the study period, only 6% died of heart attacks. Progression of HIV-related diseases was the leading cause of death.
After analyzing data from more than 23,000 patients in the U.S., Europe, and Australia who had been involved in other studies, the researchers report that the yearly death rate from heart attacks was less than 1% per year. Their findings are published in this week's New England Journal of Medicine.
This current study is the latest attempt to address growing concerns that AIDS cocktails -- and in particular, protease inhibitors, which have the strongest effect in fighting HIV infections -- can have a direct effect on boosting heart attack risk in those with HIV.
These drugs are known to increase blood cholesterol and fat levels -- as well as insulin resistance, a risk factor in diabetes and heart disease. The authors say that these effects are likely the primary mechanism for the increased risk of heart attacks they observed.
Still, more than half of the people who were studied were current or former smokers, and many had other risks factors for heart disease, such as high blood pressure. Many also had a high cholesterol level prior to taking these drugs.
When the researchers took into account all of these factors, they realized that the AIDS drugs contributed very little to the increase in risk.
The bottom line: AIDS cocktails are still worth the risk, say the researchers, led by Nina Friis-Moller, MD, of the Copenhagen HIV Programme at Hvidovre University Hospital.
"The substantial benefits of combination antiretroviral therapy continue clearly to outweigh the increased risk of myocardial infarction associated with this therapy," they write.
Agreed, say two experts who were not connected to the study but are thoroughly entrenched in research on how AIDS cocktails contribute to cardiovascular disease.
"The good news is that people with HIV are living longer, productive lives because of these drugs," says Judith Currier, MD, MSc, associate director of the UCLA Center for Clinical AIDS Research and Education, who has conducted her own studies on the association.
"Patients (getting these drugs) need to take measures, like everyone else, to lower their risk of chronic diseases -- and that includes atherosclerosis," she tells WebMD. "That means getting their lipids checked regularly, and looking at their diet, and exercise, and smoking habits in order to minimize their risk. Maybe they need to be more vigilant about it than other people, but definitely as least as much as others."
Currier calls this new study important and well done. "It contributes to our understanding and thinking about this subject. Since the more potent treatments have only been available for seven or eight years, we don't know yet about their long-term effect. But people are doing very well on these drugs, and our estimate is that this benefit will continue."
In her own research, she finds that HIV-positive patients who take protease inhibitors for at least two years have no increase in artery thickness compared with those not taking these drugs. This increased artery thickness could signal atherosclerosis, a marker for heart disease.
Some previous studies, like this new one, suggest there's a small but measurable increased risk of heart attack from newer, more potent drugs. But another major finding, published last February in TheNew England Journal of Medicine and involving some 37,000 treated with AIDS cocktails and other drugs since 1993, concludes that the "fear of accelerated vascular diseaseneed not compromise antiretroviral therapy over the short-term."
"If you look at a large enough group of patients carefully enough, there is a suggestion there may be a modest but significant increase in cardiovascular risk," says Daniel R. Kuritzkes, MD, director of AIDS research at Brigham and Women's Hospital in Boston, who wrote an editorial to the February study. "But there is an enormous benefit from antiretroviral therapy."
He tells WebMD that since combination-drug AIDS cocktails have become available, the overall death rate from AIDS has decreased between 70% and 80%.
"In the grand scheme of things, where drugs that might cause (high cholesterol) are necessary, patients will get far greater benefit from them in terms of an effect on their HIV than from their downstream risk of heart disease."