triolein and HIV-Infections

The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia.. Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35 mg/kg per day) for 2 weeks resulted in a 2-fold increase in fasting plasma triglyceride (TG) levels, which was specific for very low-density lipoprotein (VLDL). RTV did not change the hepatic VLDL-TG production. Instead, RTV did increase the postprandial TG response to an oral fat load (area under the curve, 25.5+/-12.1 versus 13.8+/-6.8 mmol/L per hour in controls; P<0.05). Likewise, RTV hampered the plasma clearance of intravenously injected glycerol tri[3H]oleate-labeled VLDL-like emulsion particles (half time, 19.3+/-10.5 versus 5.0+/-1.3 minutes in controls; P<0.05) associated with a decrease of 44% in plasma lipoprotein lipase activity. Accordingly, RTV decreased the uptake of TG-derived fatty acids (FAs) into adipose tissue, as well as the uptake of albumin-bound FA.. We conclude that RTV causes hypertriglyceridemia via decreased lipoprotein lipase-mediated clearance of VLDL-TG. In addition, RTV specifically impairs the uptake of FA in adipose tissue, which may contribute to the lipodystrophy that is frequently observed in HIV-infected subjects on antiretroviral therapy.

Topics: Adipose Tissue; Animals; Anticoagulants; Apolipoprotein E3; Apolipoproteins E; Cholesterol, VLDL; Emulsions; Enzyme Activation; Fatty Acids; Female; Heparin; HIV Infections; HIV Protease Inhibitors; Hypertriglyceridemia; Lipolysis; Lipoprotein Lipase; Mice; Mice, Transgenic; Postprandial Period; Ritonavir; Triglycerides; Triolein; Tritium

The aim of this study was to evaluate fat absorption in HIV-positive (HIV+) patients in different phases of HIV infection using a 14C-triolein breath test. We distributed 47 HIV+ patients according to the 1993 Centers for Disease Control Revised Classification: 20 in Group 2 (A1 or A2) and 27 in Group 3 (B1, B2, A3, B3, or C). Ten HIV-negative healthy subjects comprised the control group (Group 1). All individuals underwent a 14C-triolein breath test. Parasitic infection was evaluated through three stool exams, including Cryptosporidium and Isospora investigation. The median value of cumulative 6 hours' 14C excretion expressed as percentage of the 14C given as triolein was significantly higher in Group 1 (8.4%) than Group 2 (5.5%) or Group 3 (3.4%), p = 0.04 and p << 0.01, respectively. Fat malabsorption was found in 25% of Group 2 individuals, 52.6% of those without diarrhea in Group 3, and was correlated with CD4+ lymphocyte counts (p << 0.01). Fat malabsorption is a common feature in advanced stages of HIV infection, even in the absence of diarrhea and is also present in asymptomatic HIV+ patients. These findings suggest that malabsorption is an early event in HIV-infected individuals and is correlated with the degree of immunosuppression.

Topics: Adult; Breath Tests; Carbon Radioisotopes; Case-Control Studies; CD4 Lymphocyte Count; Fats; Female; HIV Infections; HIV Seropositivity; Humans; Malabsorption Syndromes; Male; Parasitic Diseases; Time Factors; Triolein