The Bay Area Reporter - June 26, 1998
Matthew Sharp, ACT UP/Golden Gate Writers Pool

A recent research letter in The Lancet describes two men as having atheroscleosis, a thickening of the walls of arteries to the heart. This is a premature condition seen in early coronary artery disease. Several care providers from Ward 86 at San Francisco General Hospital (SFGH) are not noticing such severe problems, but are concerned about elevated triglyceride and cholesterol levels, which may be warning signals for future heart problems. These reports have led to further questions about the complications in longterm survival of people with AIDS, and the side effects of antiretroviral medication.

Past Bay Area Reporter Health Perspective columns have focused on other problems that have been experienced by a number of people in the HAART era (highly active antiretroviral treatment), such as body fat redistribution, elevated liver and kidney enzymes, and buffalo hump. While these abnormalities cannot be taken lightly, heart complications should be a cause for concern given the seriousness of heart disease, even though the reports are preliminary. Plus, it is common knowledge that anyone (HIV-positive or negative) with elevated levels of triglycerides and cholesterol over time will have a downside cumulative effect on the heart.

Several questions need to be answered through clinical trials before anyone can jump to conclusions, and rush to stop their antiretrovirals. What is the cause of this condition? Is it related to longterm survival and simply growing older, or is it because of antiretroviral use? Is it only the protease inhibitors causing these abnormalities? Does body fat re-distribution have anything to do with it? Are all these problems we are seeing related to one another, and will they have a cumulative effect? How can doctors appropriately diagnose and warn patients? Are there possible treatments?

Clearly, there are many complicated overlaying factors that may mean different things. One thing is certain, however, and that is more research needs to happen. Dr. Albert Camacho, cardiologist from SFGH who has treated HIV patients for several years, stated that "I don't think it [cardiac problems] will be a big problem, at least in the short term, but I think there are more interesting issues that need to be studied around it. We need to remember where we were years ago when many more people were dying. Today people are doing better through antiretroviral therapy, and this new problem should not preclude people from stopping their HIV medications, which have brought us to where we are."

High cholesterol, triglycerides, and protease paunch

People with HIV have abnormal lipid levels in the first place. (Lipids are the fats we know as triglycerides and cholesterol. Cholesterol can be differentiated between good and bad.) Early in the epidemic Carl Grunfeld, endocrinologist from the Veterans Hospital in San Francisco, found lower levels of cholesterol, specifically LDL (low-density lipoprotein) in HIV-positive people. Lower levels of this bad cholesterol seemed a good thing, since high levels are a risk factor for heart disease. However, after combination therapy with protease inhibitors started, people were seeing levels of the bad cholesterol going up, so there seemed to be some correlation with HAART.

Also, raised levels of triglycerides, another lipid, was also becoming apparent. According to Camacho, it is not exactly known what elevated triglycerides mean in relation to heart disease. Extremely high triglycerides can cause pancreatitis, a life-threatening condition of the pancreas. But all of these reports of abnormal levels are anecdotal or observational. There are no controlled clinical studies to show proof that combination therapy causes any of these lipid abnormalities, and how they may cause heart disease.

As if abnormal lipid levels weren't enough, we are seeing fats accumulate in the abdomen, also known as "protease belly." This type of fat that is being redistributed in the gut is called "visceral fat." According to Carl Grunfeld, this visceral fat causes heart disease in HIV-negative people, so it makes sense that over time, it is not a good thing to have this type of fat accumulate in the gut.

So abnormal lipid levels, visceral fat, and the use of protease inhibitors might cause cardiac problems over time. But there seems to be a lack of knowledge and consensus among physicians and researchers about whether the drugs are causing the problem; HIV may also cause many of the lipid abnormalities.

Also, with the turnaround in the epidemic and people surviving longer, some people with HIV are reverting back to improper diets loaded with saturated fats and cholesterol, smoking, and not getting enough exercise, all risk factors for heart disease.

Research

There is work being done to sort all of this out. The Endocrinology team at SFGH, led by Morrie Schambelan and Kathy Mulligan, is looking back on data from people in the human growth hormone study. When the study began, protease inhibitors were not available. Over the course of the study, protease inhibitors were allowed and people began using them. It is hoped that some information on lipid abnormalities can be gleaned from looking back on this cohort of people, and comparing levels from before and after protease inhibitor use. The team plans on another randomized controlled study to get definitive answers on much of these problems. The AIDS Clinical Trials Group will be running numerous nested studies into existing large combination therapy trials to assess lipid metabolism, body fat redistribution, and metabolic dysfunction in general.

Camacho, the SFGH cardiologist, believes observational studies would be able to gather important information on heart problems, but warns that he doesn't treat lipid abnormalities with the statin drugs, which are used to lower cholesterol in HIV-negatives. He feels it is "extremely premature" to recommend these treatments when we don't know the whole scope of what is happening.

"In the big picture there is not a lot to worry about," Camacho said, "in light of the positive changes we've seen in the epidemic." But many PWAs who have always been assertive about treating their disease want answers to this problematic early heart condition, before more reports of heart disease surface. And the cumulative effect of all these conditions which are known to cause heart disease, leaves one wondering.
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