Reducing plasma HIV RNA improves muscle amino acid metabolism

Kevin E. Yarasheski, Samuel R. Smith, William G. Powderly

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Morgan 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 (Ra 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 Ra 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 × 10 3 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 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%/h, P = 0.01), Ra 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.

Original languageEnglish
Pages (from-to)E278-E284
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1 51-1
StatePublished - Jan 2005


  • Antiretroviral medications
  • Body composition
  • Cachexia
  • Human immunodeficiency virus
  • Lentivirus
  • Mass spectrometry
  • Metabolic complications


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