4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 22-25 September 2002, San Diego, CA, USA

BACKGROUND: We reported 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; Am J Physiol. 1998 Oct;275(4 Pt 1):E577-83). We hypothesized that high plasma HIV viraemia (VL) caused dysregulation of muscle amino acid metabolism.

OBJECTIVES: We determined whether a reduction in viral load (>1 log) increased muscle protein synthesis rate and reduced R_a gln in 10 men and one woman (22–57 years; 60–108 kg; 17–33 kg muscle) with advanced HIV (CD4=0–311 cells/µl; VL=10–375×10³ copies/ml).

METHODS: 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 4.3 ±0.6 months after initiating their first or a salvage antiretroviral therapy regimen.

RESULTS: After treatment, median CD4 increased (94 versus 137 cells/µl, P=0.021) and median VL was reduced (171,758 versus 87 copies/ml, P=0.002). Mixed muscle protein synthesis rate increased (1.5 ±0.1 versus 1.9 ±0.2 %/day, P=0.022), and R_a gln decreased (387 ±33 versus 317 ±15 µmol/kg FFM/h, P=0.038). Whole body muscle mass and maximum voluntary thigh muscle strength were only modestly increased (P=not significant). We estimate that for each 10,000-copies/ml reduction in VL, ~3 g of additional muscle protein are synthesized per day.

CONCLUSIONS: These findings suggest that high plasma viraemia reduces muscle protein synthesis and augments muscle proteolytic pathways. Reducing VL restores muscle protein synthesis and proteolysis to more normal values.

Supported by NIH grants DK54163, DK49393, DK56341, RR00954, RR00036, A120593.

Presenting author: KE Yarasheski

2002-09-22
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