People infected with the AIDS virus who take antiretroviral drugs don't appear to have an increased risk of having heart attacks or strokes, at least in the short run, according to a new study from the nation's veterans hospitals.
The issue is important because AIDS drugs, especially those in the protease inhibitor family, are known to sometimes increase blood concentrations of cholesterol, triglyceride and glucose, all of which, in turn, increase vascular disease risks.
Scattered reports of AIDS patients who controlled their viral infections, only to suffer heart attacks a few years after starting antiretroviral therapy, have circulated widely. Worry about the medicines' long-term hazards is one of the reasons that AIDS specialists recommend starting them later in the course of infection than they did in the past.
On the last day of the 9th Annual Retrovirus Conference, a researcher described the experience of 37,000 people with human immunodeficiency virus (HIV) infection treated through the Department of Veterans Affairs medical system.
From 1993 through last June, the patients had received 1.4 million prescriptions for antiretroviral drugs. They took the drugs, on average, for three years. The VA patients' death rate from all causes fell 75 percent. At the same time, hospitalizations for heart disease and stroke -- and deaths from those conditions -- dropped by 10 percent to 20 percent. The downward trend of vascular disease was also seen in subpopulations of patients at higher risk: those with existing heart problems, people over age 55, and diabetics.
"We don't think fear of vascular complications should inhibit prescribing of antiretroviral medicines," said Samuel A. Bozzette, a physician with the VA hospital in San Diego.
A study of HIV-positive men enrolled in the Northern California branch of the Kaiser Permanente HMO showed similar results. People on or off combination antiretroviral therapy, and people taking protease inhibitors or not, all had roughly the same rates of heart attack and angina over the course of five years.
As a group, however, the HIV-infected men had a somewhat higher risk of heart problems compared with uninfected men in the HMO. The risk-factor profiles of the populations were different, but that didn't seem to tip the HIV-infected men into a higher risk group. The HIV-positives, for example, were twice as likely to smoke but were less likely to have high blood pressure or diabetes. The researchers speculated that HIV infection itself may raise heart attack risk.
Support for that last hypothesis was suggested in a study done by researchers at the University of Minnesota and several other academic medical centers. In 100 randomly selected patients, they measured C-reactive protein (CRP), a bloodstream marker of inflammation known to increase a person's risk of heart attack. Half the people had CRP levels in the high-risk range -- a much greater proportion than in the general population.
The results of heart disease studies in HIV patients, however, aren't entirely consistent.
Researchers from the Centers for Disease Control and Prevention, the Dupont Circle Physicians Group and Cerner Corp. in Vienna looked at what happened to patients treated at nine HIV clinics around the country from 1993 through 2000. Among the 3,000 people taking protease inhibitors, there were 13 heart attacks, but there were only two among the 2,700 people not taking that class of drugs.
The blood vessel changes that lead to symptomatic heart disease or stroke often develop over decades, and HIV patients will probably have to be on antiretroviral drugs for a much longer time before a final answer about their risk is known. It's also possible there may be risks associated with specific drugs that are not seen even in closely related compounds.
In the conference's final session, a researcher at Indiana University described an experiment in which six healthy, uninfected men took the protease inhibitor indinavir for four weeks and were subjected to a battery of tests. The drug seemed to impair the ability of subjects' large arteries to produce nitric oxide, a substance that causes vessels to dilate in response to an organ's demand for greater blood flow.