Researchers Study Long-Term AIDS Drugs Use

Feb 18, 2004 (United Press International via COMTEX) -- A decade ago a diagnosis of HIV, which causes AIDS, meant a life expectancy of about two years. Now highly effective drug cocktails are keeping people alive far longer and doing it so well researchers are looking at the side effects long-term use of these medications may create.

It was 1996 when the era of highly active antiretroviral therapy -- combination treatments with drugs such as protease inhibitors -- began. Over time, HIV/AIDS death sentences began to be commuted to life with a long-term chronic disease.

With chronic disease, however, comes other concerns, including controversy over whether a mainstay of treatment for infection with human immunodeficiency virus -- namely protease inhibitors -- might take a toll on a patient's heart.

At the recent 11th annual Retrovirus Conference in San Francisco, researchers scrutinized the connection.

"For people who have HIV infection, the heart disease rate is twice that of people without HIV infection," said Dr. Daniel Klein, chief of infectious diseases at Kaiser Medical Center, Haywood, Calif.

Klein said there also appears to be a link between heart disease in HIV patients and protease inhibitors.

"In our analysis, we found that protease inhibitor use is an independent and significant risk factor for coronary heart disease," he said.

He said exactly how protease inhibitors affect patients and their hearts is not known but it could be due to increased cholesterol and triglyceride levels -- both implicated in the process leading to heart attacks.

"There is evidence that treatment with some of the medication used to treat HIV infection is causing increases in lipids in the blood," said Dr. Robert Bonow, chief of cardiology at Northwestern University School of Medicine in Chicago and a past president of the American Heart Association.

He told United Press International those increases in blood fats can put patients at higher risk for heart disease.

Klein reviewed records of 4,762 HIV-positive men in the Kaiser Permanente of Northern California healthcare system, and compared their heart disease and heart attack rates to 42,526 presumed non-infected other patients.

He found that among HIV positive men, the heart disease event rate was 6.3 per 1,000 person years, compared to three events per 1,000 person years among the men without HIV. He also found HIV patients suffered heart attacks at the rate of 3.7 per 1,000 person years, compared with 2.2 in the uninfected group.

The links among heart disease, HIV and HIV drugs have not gone unnoticed.

"There are those in the industry who are interested in finding medications that are equally effective in the drug's ability to limit HIV infection and to limit the impact on increases in the body fats that are related to cardiovascular disease," Bonow said.

For example, one of the newest antiretroviral treatments on the market is enfuvirtide, sold as Fuzeon, frequently prescribed for patients on long-term treatment.

Jain Chung, a researcher for Hoffman LaRoche Pharmaceuticals, Nutley, N.J., and a co-author of the research paper, said doctors used imaging techniques to see if fat accumulation increased in patients but found no differences after a year between patients taking the drug and those not taking it.

Robert Murphy, clinical professor of infectious diseases at Northwestern, said: "The mechanism of action of enfuvirtide would not be expected to cause any problems with lipids in the body. So the results of this study confirm what we would have expected."

In another study, researchers compared the effects of one of the most prescribed treatments for HIV infection -- a combination using the protease inhibitor lopinavir -- against a similar combination treatment using the protease inhibitor saquinavir.

"The major message from this trial," said Dr. Sharon Walmsley, senior scientist at Toronto General Research Institute in Canada, "is that there are no major changes in cholesterol over 48 weeks of therapy, but when you look at triglycerides there may be a more of a problem with lopinavir rather than with saquinavir."

Both treatments involve the use of another protease inhibitor, ritonavir, which is known to give a therapeutic boost to the other drugs. Walmsley said patients given lopinavir/ritonavir had a 29 percent increase in triglyceride levels over the course of the study, whereas median triglyceride levels did not increase in the saquinavir/ritonavir arm.

"We have been reporting on these links for about five years," Klein said. "It seems that the longer one is on protease inhibitors, the greater the risk of heart disease. I still believe that the link between heart disease and HIV infection may be due to the virus itself. Even for those not on protease inhibitors the heart disease rate is twice that of people with no HIV infection."

He said HIV infection involves an ongoing inflammation in the body that might also affect heart disease.

Bonow said inflammation has long been considered a possible cause of the cascade of events that leads to formation of atherosclerosis and subsequently heart disease. He said the emergence of heart disease concerns in HIV-infected individuals is "good news, bad news."

The good news, he said, is that scientists have been able to so successfully treat HIV/AIDS that now researchers have to work on the bad news -- the long-term implications of infection and its therapies.

"However, there are many good drugs that can be used to treat increases in blood fats," Bonow said. "We now have to be alert to treat HIV infection and the increases in blood lipids as aggressively as with other patients who have high cholesterol."

Klein said while a risk reduction therapy for heart disease is warranted, patients with HIV infection shouldn't give up on protease inhibitors.

"Any risks associated with protease inhibitors use must be weighed against the known benefits," he said.

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Ed Susman covers health and medical issues for UPI. E-mail sciencedesk@upi.com

Copyright 2004 by United Press International.