July 10, 2002
In the literature there is a tremendous amount of controversy as to whether HIV infection and antiretroviral medications increase the risk of heart disease. Dr. Jens Lundgren from the Copenhagen HIV Programme in Denmark presented a review and perspective on factors that contribute to coronary heart disease in HIV patients.
Dr. Lundgren started by reviewing several studies which demonstrate several limitations of the current data. He first reviewed the previous presentation's data by Barbaro et al. This was a prospective study of 1,500 patients, 750 on a protease inhibitor (PI)-containing HAART regimen and 750 on a HAART regimen without a PI that were followed for up to four years.
Although the study lost a significant number of patients in the final observation period, the results showed that PI-containing regimens were associated with significantly more cases of heart attack than non-PI regimens (9.8 versus 0.8 cases per 1,000 patient years of observation).
However, the analysis was based on only 25 heart attack cases, and there was an imprecise assessment of other risk factors that might have precipitated a heart attack, and most of the events occurred late into the trial when many of the patients had dropped out. Dr. Lundgren then presented a review of a meta analysis performed by Coplan et al. in 2000, which found that the relative risk for PI-containing regimens was 1.8 times higher than non-PI regimens (again based on 19 cases in over 10,000 patients).
Dr. Lundgren then introduced the concept of lag time. This means that during the first several months of observation in a study, there may not be any heart attacks seen. In other words, it takes many months of exposure to antiretroviral medications before an increased number of heart attacks would be seen. This was demonstrated in a recent French study shown by Dr. Lundgren. The relative risk of heart attacks only started to increase after 18 months of treatment. This could introduce bias into the observations that have been made in some of the studies. Dr. Lundgren then reviewed the U.S. HOPS data, Kaiser-Permanente data, and U.S. Veterans data. The first study demonstrated a five times greater risk of heart attack for patients on PIs, whereas the latter two studies did not show an increased risk.
Dr. Lundgren noted that the major limitations of these studies are that they are retrospective. It is hard to ascertain all heart attack events, if they happened in the past. What about patients who have heart attacks out of the hospital where they may not be documented. Data on risk factors such as smoking, diabetes, blood pressure, and prior heart problems has not systematically been collected in these studies. And there have been a low number of total events, so statistically it is difficult to map trends.
Future research should involve the prospective collection of data and the influence that specific HIV drugs, HIV factors (such as viral load and CD4+ count), drug-induced unique factors, genetic factors and non-HIV modifiable risk factors have. In addition, factors such as behavioral/lifestyle changes, switching HIV medications and treatment of metabolic abnormalities (such as lowering cholesterol/triglycerides, blood sugar and blood pressure) will also need to be accounted for in order to understand whether there is a relative increase in risk with HIV infection.
Dr. Lundgren concluded his talk by introducing the DAD study, which is a prospective study of over 18,000 patients that will be followed for over three years to determine what the real probability of a heart attack associated with HIV infection might be.
Because of the current clearly established benefits of HAART, patients should not abruptly stop their regimen because of a perceived increased risk of heart disease associated with these medicines. Focus should rather be on risk reduction of heart disease such as stopping smoking, exercise, diet modification, blood pressure control and diabetic screening and subsequent treatment if necessary.
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