HIV-Positive People on HAART Have Slightly Higher Risk of Heart Attack Than People Not on Treatment, Study Says

HIV-positive people on highly active antiretroviral therapy have a slightly higher chance of having a heart attack than HIV-positive people who are not taking the drugs, according to a study published in the Nov. 20 issue of the New England Journal of Medicine, the Washington Post reports (Brown, Washington Post, 11/20). The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group tracked 23,468 HIV-positive patients at 188 clinics in the United States, Australia and 21 European countries (DAD Study Group, New England Journal of Medicine, 11/20). The researchers tracked the patients -- some of whom were already on HAART before the study, some of whom started the therapy during the study and some of whom did not take the drugs -- for an average of 1.5 years (Washington Post, 11/20). The DAD study found that HAART was independently associated with a 26% relative increase in the rate of heart attack per year of exposure for the first four to six years on HAART (New England Journal of Medicine, 11/20). However, the absolute risk of having a heart attack was low -- for every 250 people on HAART for four years there was an average of one heart attack. The study says that the increased risk of heart attack is probably linked to a rise in cholesterol and triglyceride levels in the blood of patients on HAART (Washington Post, 11/20).

Implications
The researchers concluded that the "absolute risk of myocardial infarction was low and must be balanced against the marked benefits from antiretroviral treatment" (AFP/Yahoo! News, 11/19). The study showed that the participants on HAART "huge[ly]" benefited from the drugs, according to the Post. Overall, study participants had an average CD4+ T cell count of 226 cells/mm3 before starting HAART, according to the Post. The annual mortality rate for patients with similar counts is about 22% without treatment but about 2% with treatment, Dr. Jens Lundgren of Hvidovre University Hospital in Copenhagen, Denmark, one of the study authors, said. The increased risk of heart attack for people on HAART is "not a major problem at the moment," Lundgren said, adding, "But, of course, the question is: How are (these patients) going to look over time as they grow old and they are no longer dying of HIV disease? We know that age is a major risk factor for cardiovascular disease." The average age of the study participants was 39, according to the Post (Washington Post, 11/20). The rate of heart disease in the age group studied is relatively low, according to Reuters (Reuters, 11/19). Fred Gordin, an AIDS specialist at the Veterans Affairs Medical Center in Washington, D.C., said that the findings reinforce a trend in HIV care to start HAART later in the course of infection when CD4+ cell counts are in the 300 cells/mm3 to 400 cells/mm3 range.

Reaction
"In my mind, [the study findings] settl[e] whether or not there is a link [between HAART and an increased risk of cardiovascular events]. There is a link. It's now a matter of fine-tuning how much there is," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who was not involved in the study, said (Washington Post, 11/20). However, the findings contradict those of a study published in the Feb. 20 issue of NEJM, which did not find a similar risk (AFP/Yahoo! News, 11/19). Dr. Samuel Bozzette of the San Diego Veterans Affairs Medical Center and colleagues from Johns Hopkins Bloomberg School of Public Health in a retrospective study of almost 37,000 HIV-positive patients found that antiretroviral drugs did not cause premature heart attack or stroke (Kaiser Daily HIV/AIDS Report, 2/21). The two studies may have reached different conclusions because both lacked control groups of HIV-negative people, Peter Sklar of the Division of HIV/AIDS Medicine at Drexel University College of Medicine and Henry Masur of the NIH Critical Care Medicine Department of the Warren Grant Magnuson Clinical Center write in an editorial accompanying the current study (Reuters, 11/19). Sklar and Masur say that although antiretroviral therapy has been "among the miracles of recent decades ... we must work toward mitigating the toxic effects that have the potential to diminish the quality and duration of patients' survival over the long term" (BBC News, 11/20). However, because of the complexity of the medical care of HIV-positive people, "unequivocal evidence" is needed to warrant "changes in our successful treatment paradigm," Sklar and Masur conclude (Sklar/Masur, New England Journal of Medicine, 11/20).