Protease inhibitors are associated with higher levels of fibrinogen, a clotting factor linked to coronary artery disease, according to a study by researchers at the San Francisco VA Medical Center, who say the findings are the first to demonstrate a possible reason for the previously observed association between the meds and an increased risk of heart attacks.

At the same time, the study also shows a link between another common HIV treatment, non-nucleoside reverse transcriptase inhibitors (NNRTIs), and lower fibrinogen levels. The study appears in the March 30, 2008 issue of AIDS.

“Most of the patients we treat for HIV/AIDS are at low risk for heart disease,” says senior investigator Carl Grunfeld, a staff physician at SFVAMC and professor of medicine at the University of California, San Francisco. “But for patients who are at high risk, physicians might want to consider starting them on NNRTI therapy rather than PI therapy. For patients already on PI therapy, physicians might consider prescribing aspirin for its anti-clotting properties, since fibrinogen is a clotting factor, as well as aggressively treating cholesterol levels, since clots attach to cholesterol plaques.”

The study analyzed blood samples from 1,131 HIV-infected participants and 281 controls in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, an ongoing nationwide longitudinal study of the metabolic effects of modern highly active antiretroviral therapy (HAART). Median fibrinogen levels were 11 percent higher in HIV-infected subjects taking any PI than in those not on a PI, and 11 percent higher than in controls.

Among HIV infected subjects taking any NNRTI, median fibrinogen levels were nearly 9 percent lower compared with those not on an NNRTI, and almost 10 percent lower than controls. The researchers observed these associations after controlling for other risk factors associated with higher fibrinogen, including age, race, smoking, and HIV viral load.

Among HIV infected subjects taking PIs and NNRTIs together, median fibrinogen levels were similar to controls. “This indicates that NNRTIs counteract the effects of PIs in raising fibrinogen levels,” says Grunfeld. However, he notes that PIs and NNRTIs usually are not prescribed together anymore because studies have indicated that they are more efficacious and less toxic when prescribed separately.

Grunfeld says the study has implications for treatment of HIV/AIDS patients as they age, “because the greatest risk factor for heart disease is age. If you’ve got a patient on protease inhibitors, this tells you that you have to watch their cholesterol very carefully. You need to consider heart disease risk when picking an HIV therapy regimen.”