July 14, 2009
The astounding success of the anti-HIV drug cocktails known as HAART, which have dramatically raised the life expectancy of people with HIV/AIDS, is undeniable. But as the population of HIV-positive people ages worldwide -- the number of people aged 50 and older living with HIV in the U.S. alone has increased 77 percent from 2001 to 2005 -- there is an appropriate focus on the side effects of these medications. After all, people with HIV are living longer and are therefore taking these medications for many years. In addition, aging is generally associated with serious health conditions that are increasingly prevalent. The concerns about HIV medication will only grow as new treatment guidelines are expected to recommend initiating HAART earlier in the course of infection. amfAR grantee Dr. Steven Deeks and colleagues, working at the University of California, San Francisco, report in the June issue of AIDS on their study of the relationships between HIV, anti-HIV drugs, and the risk of developing heart disease.
These investigators followed a unique group of individuals known as "elite controllers," people who are HIV positive but, in the absence of treatment, maintain undetectable viral loads and normal T-cell counts. They were compared to three other groups: those who were HIV positive but untreated; those who were HIV positive and on various HAART regimens; and age-matched HIV- negative subjects. Blood tests were performed to track levels of immune hormones and markers of inflammation, along with sonogram-based tests of the thickness of the wall of the carotid artery, the major blood vessel of the neck. These tests are known to help predict which individuals are more prone to heart attacks and strokes.
Deeks and colleagues found that increased thickness of the carotid artery wall and higher levels of certain blood proteins (IL-6 and CRP) -- all risk factors for heart disease -- were strongly associated with HIV infection regardless of whether the infection was being treated. Taking HAART was associated with an additional risk for these differences in carotid thickness and inflammation.
These differences could not be attributed to age, smoking history, blood sugar levels, or blood pressure. In addition, even though certain anti-HIV drugs are known to elevate "bad" cholesterol, the increases in carotid artery wall thickness and blood protein levels were independent of changes in blood cholesterol and lipids.
Based on these data and other recent studies, the authors suggest that the high level of immune activation -- a hallmark of HIV disease that is already present within days of infection -- is responsible for these changes that can leave an individual at increased risk for heart disease. This activation state may be a consequence of the early destruction of gut tissues by HIV, characteristic of elite controllers as well as individuals with uncontrolled infection.
None of this means that a person should avoid HIV treatment because of concern about having a heart attack or stroke. The number of such cases caused by HAART is thought to be quite low. But it does suggest the need for more research into improving the side effect profile of HAART and, as the authors conclude, "our observations suggest that all HIV-infected individuals -- even those doing apparently well with or without antiretroviral treatment -- may benefit from aggressive cardiovascular risk management and perhaps the use of anti-inflammatory agents such as statins, although this remains unproven treatment in this setting."