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TRANSLATIONAL PHYSIOLOGY

Reducing plasma HIV RNA improves muscle amino acid metabolism

Department of Internal Medicine, Division of Metabolism, Endocrinology and Lipid Research, and Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri

Submitted 6 August 2004 ; accepted in final form 7 September 2004

We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577–E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (R_a Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (1 log) increased muscle protein synthesis rate and reduced R_a Gln and muscle proteasome activity in 10 men and 1 woman (22–57 yr, 60–108 kg, 17–33 kg muscle) with advanced HIV (CD4 = 0–311 cells/µl; HIV RNA = 10–375 x 10³ copies/ml). We utilized stable isotope tracer methodologies ([¹³C]Leu and [¹⁵N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma R_a 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%/h, P = 0.01), R_a Gln decreased (387 ± 33 vs. 323 ± 15 µmol·kg fat-free mass^–1·h^–1, 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 = not significant). 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.

human immunodeficiency virus; metabolic complications; body composition; mass spectrometry; antiretroviral medications; cachexia; lentivirus

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