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

Abstract

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 (PIϩ, 7 patients) or without PIs (PIϪ, 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-[1-13 C]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 Ͻ 0.05) less negative in the PIϩ than in the PIϪ group. In HIV-infected patients treated with PIs, the oxidative leucine disposal during an acute amino acid-glucose infusion was lower (0.58 Ϯ 0.09 vs. 0.81 Ϯ 0.07 mol ⅐ kg FFM Ϫ1 ⅐ min Ϫ1 using plasma [ 13 C]leucine enrichment, P ϭ 0.06; or 0.70 Ϯ 0.10 vs. 0.99 Ϯ 0.08 mol ⅐ kg FFM Ϫ1 ⅐ min Ϫ1 using plasma [ 13 C]ketoisocaproic acid enrichment, P ϭ 0.04 in PIϩ and PIϪ groups, respectively) than in patients treated without PIs. Consequently, whole body nonoxidative leucine disposal (an index of protein synthesis) and leucine balance (0.50 Ϯ 0.10 vs. 0.18 Ϯ 0.06 mol ⅐ kg FFM ⅐ Ϫ1 ⅐ min Ϫ1 in PIϩ and PIϪ groups respectively, P Ͻ 0.05) were significantly improved during amino acid-glucose infusion in patients treated with PIs.

Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins

“…This equation for S PSS is the same as derived by Macallan et al [3] including Garlick, by Tauveron et al [12], and by Prod'homme et al [10]. One difference is that, in those publications, the expressions for Q and for X do not include a subtraction for the tracer infusion rate i: Q = iE i /E p and X = x/E p , identical to the formulas used in a radiotracer study, noting that iE i corresponds to the radioactivity infusion rate.…”

“…Investigators who assume a PSS should use the equations from Garlick and coworkers instead [Eqs. (10), (11), and (29)]. Both sets of equations, as derived here, account for preinfusion enrichment.…”

“…1C shows a second possibility-PSS. This was articulated first by Garlick et al [9] and is used by only a few groups [3,10]. Under this assumption, protein synthesis is unaltered by the infusion of a single amino acid because the levels of the other 19 amino acids involved in protein synthesis are not affected by the infusion.…”

HIV and Highly Active Antiretroviral Therapy: Dyslipidemia, Metabolic Aberrations, and Cardiovascular Risk

“…Under these conditions, an increase in protein turnover has been demonstrated 35,37,39 . During HAART, PI therapy may favor protein anabolism by increasing protein synthesis, decreasing protein breakdown, and decreasing amino acid oxidation in HIV‐positive asymptomatic patients or patients experiencing wasting 40,41 …”

“…It is suggested that protein and amino acid metabolism are affected in different ways in muscle, liver, and adipose tissue in HIV/HAART 41 . Using muscle biopsies, it was shown that muscle protein synthesis rate and proteolysis rate were significantly increased in HIV‐positive asymptomatic patients, while they were lower in HIV‐positive patients with wasting and in control subjects 35 .…”