Controversy Surrounding Link Between HAART & Heart Disease
"New Research Confirms Role of Heart Disease as a Treatment By-
AIDS Alert (01.01.03) Vol. 18; No. 1
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, MD,
PhD, 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."
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, MD, 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, MD, 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 toDavid Haas, MD, 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.