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Whole body leucine flux in HIV-infected patients treated with or without protease inhibitors

¹Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Clermont-Ferrand/Theix, Saint-Genès-Champanelle and Centre de Recherche en Nutrition Humaine, Clermont-Ferrand; ²Service des Maladies Infectieuses et Tropicales and ³Service d’Endocrinologie et Maladies Métaboliques, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France

Submitted 17 February 2005 ; accepted in final form 19 October 2005

The present study was carried out to assess the effects of protease inhibitor (PI) therapy on basal whole body protein metabolism and its response to acute amino acid-glucose infusion in 14 human immunodeficiency virus (HIV)-infected patients. Patients treated with PIs (PI+, 7 patients) or without PIs (PI–, 7 patients) were studied after an overnight fast during a 180-min basal period followed by a 140-min period of amino acid-glucose infusion. Protein metabolism was investigated by a primed constant infusion of L-[1-¹³C]leucine. Dual-energy X-ray absorptiometry for determination of fat-free mass (FFM) and body fat mass measured body composition. In the postabsorptive state, whole body leucine balance was 2.5 times (P < 0.05) less negative in the PI+ than in the PI– group. In HIV-infected patients treated with PIs, the oxidative leucine disposal during an acute amino acid-glucose infusion was lower (0.58 ± 0.09 vs. 0.81 ± 0.07 µmol·kg FFM^–1·min^–1 using plasma [¹³C]leucine enrichment, P = 0.06; or 0.70 ± 0.10 vs. 0.99 ± 0.08 µmol·kg FFM^–1·min^–1 using plasma [¹³C]ketoisocaproic acid enrichment, P = 0.04 in PI+ and PI– groups, respectively) than in patients treated without PIs. Consequently, whole body nonoxidative leucine disposal (an index of protein synthesis) and leucine balance (0.50 ± 0.10 vs. 0.18 ± 0.06 µmol·kg FFM·^–1·min^–1 in PI+ and PI– groups respectively, P < 0.05) were significantly improved during amino acid-glucose infusion in patients treated with PIs. However, whereas the response of whole body protein anabolism to an amino acid-glucose infusion was increased in HIV-infected patients treated with PIs, any improvement in lean body mass was detected.

leucine kinetics; protease inhibitor therapy; human immunodeficiency virus infection; amino acid requirements