Protease inhibitors (PIs) are associated with increased blood levels of fibrinogen—a marker of heart disease risk—whereas non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with decreased blood levels of fibrinogen, according to a study published in the March 30 issue of AIDS.
Previous studies have found that PIs modestly increase the risk of heart attacks in HIV-positive people. The increased risk was found to be independent from changes to cholesterol, triglycerides and blood sugar, leading researchers to question if there is a stronger association between PI use and other markers of cardiovascular disease.
Erin Madden, MPH, from the University of California, San Francisco, and her colleagues theorized that increased blood levels of fibrinogen may help explain the increased heart attack risk of PIs. High levels of fibrinogen—a protein that plays a key role in blood clotting—have been strongly correlated with atherosclerosis, the buildup of fat and scar tissue in blood vessels that increases the risk of heart disease and heart attacks.
Madden’s team worked with data involving 1,131 people with HIV enrolled in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, compared with data from HIV-negative volunteers enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Madden’s group found that people who were on a treatment regimen containing a PI had fibrinogen levels that were 11 percent higher than those seen in the HIV-negative control group. People taking an NNRTI-based regimen had fibrinogen levels that were 10 percent lower than the control group. People taking a regimen containing both a PI and an NNRTI had fibrinogen levels roughly equal to the control group.
After controlling for multiple factors, people taking the PIs Crixivan (indinavir) and Norvir (ritonavir) had the strongest association with increased fibrinogen levels. People using low-dose Norvir to boost Crixivan levels had fibrinogen levels that were 8 percent higher than people taking Crixivan without Norvir. Conversely, Viramune (nevirapine) and efavirenz (found in Sustiva and Atripla) were independently associated with having decreased fibrinogen levels.
Madden’s team concludes that the increased risk of heart attacks seen with PIs in other studies may be due to the PIs’ potential to worsen atherosclerosis. The team also says that the data suggest NNRTIs may have a protective effect, but that further studies looking at the impact of individual antiretroviral drugs on fibrinogen and other markers of atherosclerosis are needed to confirm their findings.
