New Research Confirms Role of Heart Disease as a Treatment By-Product
February 7, 2003
Recent studies have shown that certain protease inhibitors and other HIV medications can lead to metabolic changes associated with heart disease. "In the past couple of years, there's been increasing concern about atherosclerosis and coronary heart disease in patients with antiretroviral therapy," said Marshall Glesby, M.D., Ph.D., assistant professor of medicine at Weill Medical College at Cornell University in New York City. "The most carefully studied patients have a number of abnormalities associated with heart disease," he continued, "including abnormal lipids, changes in body shape, diabetes, increased truncal fat, and others."Adapted from:
Research presented at the 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, held in September 2000 in San Diego, added to the body of evidence that antiretroviral therapy can lead to hypertriglyceridemia. Research has also found that patients taking regimens including the nucleoside reverse transcriptase inhibitor stavudine were at increased risk of hypertriglyceridemia.
Paul Sax, M.D., clinical director of the HIV Program at Brigham & Women's Hospital and a medical professor at Harvard Medical School-Boston, said other long-term problems associated with the drugs are morphologic changes such as gynecomastia and a dorsocervical fat pad. NRTIs are associated with fat wasting or fat atrophy, and some NRTIs are associated with peripheral neuropathy. PIs are associated with increased insulin resistance, according to Sax. When PIs and NRTIs are combined in therapy, fat cell wasting accelerates due to fat cell apoptosis. NRTI therapy can also cause lactic acidosis.
Although current research has provided seemingly solid evidence of the link between PIs and symptoms associated with heart disease, investigators do not agree on whether or not HIV patients treated with PIs run an increased risk of death from heart disease.
"Several studies say there's an increased risk with PI use, and others don't," said Judith Currier, M.D., associate professor of medicine at the David Geffen School of Medicine at the University of California-Los Angeles and director of the clinical trials unit of the UCLA Care Center. "What we need to focus on now is trying to determine to which extent it's due to HIV in itself, the metabolic changes associated with treatment or the prevalence of other risk factors for cardiovascular disease that exist in this population." Dr. Currier spoke about coronary heart disease and PIs at the 40th annual meeting of the Infectious Diseases Society of America, held in October 2002 in Chicago.
"We HIV specialists are unanimous in agreeing that people with AIDS need therapy," Sax said. "But the important thing is to be aware of the side effects so that you can treat them and manage them if necessary."
CDC recently released data showing that HIV-patients' longevity has increased since the advent of PIs and other potent antiretroviral drugs. Guidelines issued in the past year by the International AIDS Society USA and the Adult AIDS Clinical Trials Group are designed to assist HIV clinicians in decisions about managing lipid disorders and metabolic complications.
A new PI, atazanavir, currently available in expanded access programs but awaiting FDA approval, may be an alternative to antitretrovirals that cause metabolic problems, according to David Haas, M.D., director of Vanderbilt AIDS Clinical Trials Center and associate professor of medicine at the Vanderbilt Medical School-Nashville. New research shows the once-a-day drug to have favorable lipid profiles in HIV patients.
01.01.03; Vol. 18; No. 1