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1 Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Metabolism, Endocrinology & Lipid Research, Washington University School of Medicine, USA; Division of Infectious Diseases, Washington University School of Medicine, USA
* To whom correspondence should be addressed. E-mail: key{at}im.wustl.edu.
We reported that AIDS-muscle wasting was associated with an inappropriately
low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra
gln; Am J Physiol.1998;275:E577-83). We hypothesized that high plasma HIV RNA
caused dysregulation of muscle amino acid metabolism. We determined if a reduction in
HIV RNA (
1 log) increased muscle protein synthesis rate, reduced Ra gln and muscle
proteasome activity in 10 men and 1 woman (22-57yrs; 60-108kg; 17-33kg muscle) with
advanced HIV (CD4=0-311 cells/µl; HIV RNA=10-375 x103copies/ml). We utilized stable
isotope tracer methodologies (13C-leu & 15N-gln) to measure the fractional rate of mixed
muscle protein synthesis and plasma Ra gln in these subjects before and 4 mo after
initiating their first or a salvage antiretroviral therapy regimen. After treatment, median
CD4 increased (98 vs 139 cells/µl; P=0.009) and median HIV RNA was reduced
(155,828 vs 100 copies/ml; P=0.003). Mixed muscle protein synthesis rate increased
(0.062 ± 0.005 vs 0.078 ± 0.006 %/hr; P=0.01), Ra gln decreased (387±33 vs 323±15
µmol/kg FFM/hr; P=0.04), and muscle proteasome chymotrypsin-like catalytic activity
was reduced 14% (P=0.03). Muscle mass was only modestly increased (1 kg; P=ns).
We estimated that for each 10,000-copies/ml reduction in HIV RNA, ~3 g of additional
muscle protein are synthesized per day. These findings suggest that reducing HIV RNA
increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein
synthesis relative to whole body protein synthesis rate is not restored to normal, so
muscle mass is not substantially increased.
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