Likely Reason Shown for Link Between HIV Drugs and Heart Attacks

By Steve Tokar Protease inhibitors (PIs), a class of drugs commonly used in HIV therapy, are associated with higher levels of fibrinogen, a clotting factor linked to coronary artery disease, according to a study led by researchers at the San Francisco VA Medical Center. The study is the first to demonstrate a possible reason for the previously observed association between PI therapy and an increased risk of heart attacks, says senior investigator Carl Grunfeld, MD, PhD, a staff physician at SFVAMC and professor of medicine at the University of California, San Francisco. 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. "Most of the patients we treat for HIV/AIDS are at low risk for heart disease," say Grunfeld. "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 appears in the March 30, 2008 issue of AIDS. 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." Co-authors of the paper were Erin Madden, MPH, of the Northern California Institute for Research and Education, San Francisco; Grace Lee, MD, of UCSF and SFVAMC; Donald P. Kotler, MD, of St. Lukes-Roosevelt Hospital Center and Columbia University, New York; Christine Wanke, MD, of Tufts University, Boston; Cora E. Lewis, MD, MPH, of University of Alabama, Birmingham; Russell Tracy, PhD, of University of Vermont, Burlington; Steven Heymsfield, MD, of Merck Research Laboratories, Rahway, NJ; Michael G. Shlipak, MD, MPH, of SFVAMC and UCSF; Peter Bacchetti, PhD, of UCSF, and Rebecca Scherzer, PhD, of NCIRE. The research was supported by funds from the National Institutes of Health. NCIRE - the Veterans Health Research Institute - is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC. SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF. UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.