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4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV


22-25 September 2002, San Diego, CA, USA



MUSCLE SPECIFIC STRENGTH, INTRAMUSCULAR ENERGY METABOLISM, AND OTHER INDICES OF MITOCHONDRIAL FUNCTION ARE NOT ALTERED IN HIV-INFECTED PATIENTS WITH MARKED PERIPHERAL LIPOATROPHY

Antiviral Therapy 2002; 7:L12 (abstract 19)

GK Sakkas1,2, K Mulligan1,2, M daSilva1,2, J Kent-Braun3, T Schleich4, and M Schambelan1,2
1University of California, San Francisco, Calif., USA; 2San Francisco General Hospital, San Francisco, Calif., USA; 3University of Massachusetts, Mass., USA; 4University of California, Santa Cruz, Calif., USA

BACKGROUND: It has been suggested that lipoatrophy (LA) in patients with HIV infection may be a manifestation of mitochondrial toxicity. Although evidence of mitochondrial damage has been seen in muscle tissue taken from patients with LA, the functional consequences of possible mitochondrial alterations have not been studied.

METHODS: We compared non-invasive measures of muscle specific strength and intramuscular energy metabolism, as well as other indices of mitochondrial function, in six men with objective evidence of severe LA and six with normal body fat content identified in a cohort of patients undergoing baseline DEXA and magnetic resonance imaging (MRI) and spectroscopy (MRS) studies prior to a trial of creatine treatment. Data are the mean ±SE.

RESULTS: Those with LA had marked fat depletion in thigh, lower leg, and gluteal regions (33 ±3 vs 103 ±10, 3 ±1 vs 12 ±1, 88 ±5 vs 200 ±10 cm2, respectively; all P<0.001) by cross-sectional MRI and significantly less total body fat (4.0 ±0.4 vs 9.0 ±0.9 kg/m; P<0.001) and appendicular fat (1.1 ±0.1 vs 3.7 ±0.4 kg/m; P<0.001) by DEXA. However, total and appendicular lean body mass did not differ significantly between groups (31.2 ±2.2 vs 31.9 ±0.3 and 14.0 ±1.2 vs 14.7 ±0.1 kg/m, respectively). Patients with LA were older (48 ±3 vs 37 ±3 years; P=0.02) and had lower total muscle cross-sectional area in the calf (CSA, 54 ±4 vs 70 ±4 cm2; P=0.02) but not in the tibialis anterior (TA) (10 ±1 vs 11 ±1 cm2). More importantly, there were no significant differences in dorsiflexor force generated in a maximum voluntary contraction (MVC, 252 ±20 vs 292 ±9 Newtons [N]; P=0.10) or in specific strength in the TA (MVC/CSA, 25.4 ±1.7 vs 27.2 ±2.6 N/cm2; P=0.59). Resting phosphocreatine/inorganic phosphate ratio and intracellular pH by 31P-MRS did not differ significantly between groups nor did plasma lactate, serum anion gap, AST, or ALT levels.

CONCLUSIONS: In this small group of subjects with severe LA, there is no evidence of reduced muscle specific strength, or alterations in intramuscular energy metabolism or indices of mitochondrial function.

This work was supported by grants from the National Institutes of Health (AT00491, DK45833, DK54615, RR-00083).

Presenting author: GK Sakkas

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2002-09-22
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