The Body PRO Covers: The 1st International AIDS Society Conference on HIV Pathogenesis and Treatment
July 10, 2001
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- Combined Antiretroviral Therapy Causes Cardiomyopathy (Abstract 94)
Speaker: W. Lewis
Authored by Lewis, W.; Haase, C.; Raidel, S.; Russ, R.; Sutliff, R.; Samarel, A.; Emory University, Atlanta, Georgia, United States
HIV-infected children have a wide variety of cardiac disturbances, of which cardiomyopathy is the most prevalent. Although cardiomyopathy is less common in HIV infected adults, clinically apparent cardiomyopathy does occur. Subclinical cardiomyopathy has also been detected by echocardiography. Thus, it would be important to learn if antiviral therapy may be a cause of cardiomyopathy. This study, however, does not have much relevance to our patients.
Using a transgenic mouse model in which the mice express HIV proteins, but not infectious virions, these investigators set out to find out if transgenic mice given HAART developed cardiomyopathy. They treated normal mice and transgenic mice with AZT, 3TC and indinavir and found cardiac abnormalities by echo, biopsy and by biochemical evidence of heart failure in the transgenic mice given HAART, but not in the other groups. There were data presented that suggested mitochondrial damage.
Here is the kicker though: The dose of AZT used was 20-30 times higher than human exposure. AZT is known to cause muscle toxicity at higher doses, including the doses used in the early trials (up to 2,400mg/day). When asked by an audience member if he thought the model was clinically relevant, the author equivocated. I won't. While the science was interesting, the use of an unusual transgenic mice and industrial doses of AZT make this study of little relevance to our patients. Studies in chronically infected animals using exposures similar to normal clinical exposures would be of interest.
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