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Abstract
COMBINED ANTIRETROVIRAL THERAPY CAUSES CARDIOMYOPATHY
LEWIS W, HAASE C, RAIDEL S, RUSS R, SUTLIFF R, SAMAREL A
Background: Highly active antiretroviral therapy (HAART) for AIDS is implicated in cardiomyopathy (CM) and reported to cause elevated plasma lactate (LA) through mechanisms of mitochondrial dysfunction.
Methods: To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3 delta gag/pol) and wild type FVB/n (WT) littermates were treated with a HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 35 days or 10 days. At termination of the respective experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor (ANF) and sarcoplasmic calcium ATPase (SERCA2)), and determination of plasma lactate. Myocardial histology was analyzed semi-quantitatively and results were confirmed by transmission electron microscopy.
Results: LV mass increased 160% after 35 days and 92% after 10 days in the respective TG+HAART cohorts. ANF mRNA increased 260% and SERCA2 mRNA decreased 60% after 35 days in the TG+HAART cohort. LA was elevated significantly (8.5±2.0 mM) in that cohort, but not in any 10 day cohort. Microscopically, granular changes were found in the cytoplasm of cardiac myocytes in the 35 day TG+HAART cohort and mitochondrial damage was confirmed ultrastructurally.
Conclusions: Data indicate that HAART caused mitochondrial CM in AIDS TGs that worsens cumulatively.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
94
Suggested Citation
"LEWISW, et al.
COMBINED ANTIRETROVIRAL THERAPY CAUSES CARDIOMYOPATHY.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
94"
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