Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy.
BACKGROUND
Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen in patients receiving antiretroviral combination therapy (ART). However, the underlying mechanisms and long-term risks (e.g., cardiovascular events) are still unclear.


OBJECTIVE
In 5 patients with ART-associated dyslipidemia, stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days was used to investigate the metabolism of apolipoprotein B-containing lipoproteins (very low density lipoproteins [VLDL]1, VLDL2, intermediate density lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with those in 6 healthy normolipidemic controls.


RESULTS
The patients under ART showed significantly increased fasting triglycerides (359 vs. 77 mg/dl) and VLDL (54 vs. 15 mg/dl), compared with controls. They had significantly higher total cholesterol (213 vs. 157 mg/dl) and there was a nonsignificant trend toward higher LDL (136 vs. 93 mg/dl), and toward lower HDL (26 vs. 46 mg/dl). The ratio of large, buoyant LDL1 over small, dense LDL2 was markedly reduced in patients under ART (0.80 vs. 2.00). Total apo B synthesis was significantly increased (25.5 vs. 14.5 mg/kg/d) and shifted toward triglyceride rich VLDL1 (18.5 vs. 8.7 mg/kg/d) in patients receiving ART. There was also a significantly reduced rate of apo B lipoprotein transfer from VLDL1 to VLDL2 (3.7 vs. 20.7 pools/d). In addition, all patients revealed insulin resistance.


CONCLUSIONS
These data indicate that increased triglycerides in HIV-infected patients with ART are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase-mediated delipidation. In addition, total apo B synthesis was increased and shifted toward triglyceride-rich VLDL1. Overall, this lipoprotein profile in patients with ART-associated dyslipidemia implies an increased risk for cardiovascular events.
Schmitz
M
M
Institut für Klinische Chemie and Medizinische Poliklinik, Dresden, Germany.
Michl
G M
GM
Walli
R
R
Bogner
J
J
Bedynek
A
A
Seidel
D
D
Goebel
F D
FD
Demant
T
T
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001055:Apolipoproteins B / Q000378:metabolism*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced* / Q000378:metabolism; D007333:Insulin Resistance; D007700:Kinetics; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D001055:Apolipoproteins B; D008074:Lipoproteins; D018894:Reverse Transcriptase Inhibitors