October 26, 2002
It remains unclear whether HIV and/or its therapy may lead to premature coronary heart disease (CHD). There have been increasing reports of metabolic abnormalities (hyperlipidemia, glucose disturbances, fat accumulation, fat wasting) occurring in HIV-infected individuals on antiretroviral therapy, however, the long-term consequences of these remain to be defined.
Prospective observational cohorts are currently underway. In the absence of definitive data, it seems prudent to treat these metabolic abnormalities in the HIV-infected population as one does for the HIV-uninfected population. The difficulty in choosing therapeutic strategies for metabolic abnormalities is that there is limited data on the safety and efficacy of these treatment strategies but also because we have little understanding of the pathophysiology of these metabolic complications.
One way to help determine whether these metabolic complications are, in fact, potentially leading to premature coronary heart disease would be to evaluate patients for subclinical atherosclerosis. A new technology called electron beam computerized tomograpy (EBCT) can measure the amount of calcification in the lining of the blood vessels. Coronary arterial calcification (CAC) has been shown to be a marker of atherosclerosis and can help predict those at greatest risk for development of coronary heart disease and, potentially, a future cardiac event in an HIV-uninfected patient.
Dr. David Parenti presented the results of a small intriguing study evaluating the electron beam computerized tomograpy results from 39 HIV-infected men without any cardiac symptoms who have been on a protease inhibitor (PI)-containing regimen for at least 24 months. The mean age of the patients was 47 years old and they had the following traditional cardiac risk factors: 33 percent tobacco use, 18 percent hypertension, 34 percent body mass index greater than 27 and 23 percent on lipid-lowering therapy with a statin. None of the subjects had diabetes. The mean CD4+ T-cell count was 566. The mean duration of protease inhibitor use was 51 months and 51 percent had been on a boosted protease inhibitor for a mean of 22 months. The mean coronary arterial calcification scores were compared with age-matched historic controls (published data from other studies calculating coronary arterial calcification scores in asymptomatic HIV-uninfected men).
Interestingly, Dr. Parenti reported that there was a significant difference in coronary arterial calcification scores between patients on boosted protease inhibitors compared with single protease inhibitor use but yet there was no association between coronary arterial calcification scores and the duration of time someone was on a protease inhibitor.
Fifty-six percent of HIV-infected subjects had positive coronary arterial calcification score (greater than or equal to 1). Thirty-seven percent of those patients on a single protease inhibitor regimen had a positive coronary arterial calcification score, compared to 75 percent of those on a double protease inhibitor regimen (p = 0.025). There was no significant difference in age between the single protease inhibitor and double protease inhibitor groups. There appears to be only modest differences in coronary arterial calcification scores between protease inhibitor-treated patients and asymptomatic controls. Although Dr. Parenti concluded that these findings suggest that double protease inhibitor regimens may lead to accelerated atherosclerosis, several attendees expressed their concern at basing a conclusion on a small sample size.
I believe this is a step in the right direction to assist us in understanding the significance of the metabolic derangements we are seeing. In the ideal study, it would have been best to have a control group matched not only for age but for all traditional risk factors and to follow this cohort prospectively. It is difficult to interpret a small sample size with many confounding factors including different regimens. Nevertheless, it is from small pilot studies such as this that beg us to perform larger more definitive studies.
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