Influence of protease inhibitor therapy on lipoprotein metabolism
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Influence of protease inhibitor therapy on lipoprotein metabolism. / Berthold, H K; Parhofer, K G; Ritter, M M; Addo, M; Wasmuth, J C; Schliefer, K; Spengler, U; Rockstroh, J K.
In: J INTERN MED, Vol. 246, No. 6, 12.1999, p. 567-75.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of protease inhibitor therapy on lipoprotein metabolism
AU - Berthold, H K
AU - Parhofer, K G
AU - Ritter, M M
AU - Addo, M
AU - Wasmuth, J C
AU - Schliefer, K
AU - Spengler, U
AU - Rockstroh, J K
PY - 1999/12
Y1 - 1999/12
N2 - OBJECTIVES: Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper- and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV-infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options.DESIGN: We investigated prospectively, in 19 subsequent HIV-positive male patients (mean age 42 +/- 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7-40) weeks. 12 patients were treatment-naive; 7 had already NRTI medication at baseline.RESULTS: Total cholesterol increased by 28 mg dL-1 (95% CI: + 7 to + 48, baseline 158 +/- 53, P = 0.01), triglycerides increased by 96 mg dL-1 (+ 22 to + 170, baseline 152 +/- 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL-1 (+ 9 to + 31, baseline 33 +/- 21, P = 0.001), VLDL triglycerides increased by 86 mg dL-1 (+ 22 to + 150, baseline 128 +/- 91, P = 0. 01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 +/- 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (-0.02 to -0.09, baseline 0.47 +/- 0.11, P = 0.005). (Conversion factors, mg dL-1 to mmol L-1: 0.0259 for cholesterol, 0.0114 for triglycerides.)CONCLUSIONS: The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride-containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.
AB - OBJECTIVES: Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper- and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV-infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options.DESIGN: We investigated prospectively, in 19 subsequent HIV-positive male patients (mean age 42 +/- 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7-40) weeks. 12 patients were treatment-naive; 7 had already NRTI medication at baseline.RESULTS: Total cholesterol increased by 28 mg dL-1 (95% CI: + 7 to + 48, baseline 158 +/- 53, P = 0.01), triglycerides increased by 96 mg dL-1 (+ 22 to + 170, baseline 152 +/- 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL-1 (+ 9 to + 31, baseline 33 +/- 21, P = 0.001), VLDL triglycerides increased by 86 mg dL-1 (+ 22 to + 150, baseline 128 +/- 91, P = 0. 01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 +/- 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (-0.02 to -0.09, baseline 0.47 +/- 0.11, P = 0.005). (Conversion factors, mg dL-1 to mmol L-1: 0.0259 for cholesterol, 0.0114 for triglycerides.)CONCLUSIONS: The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride-containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.
KW - Adult
KW - CD4 Lymphocyte Count
KW - HIV Protease Inhibitors/therapeutic use
KW - HIV Seropositivity/blood
KW - Humans
KW - Indinavir/therapeutic use
KW - Lipoproteins/blood
KW - Male
KW - Middle Aged
KW - Nelfinavir/therapeutic use
KW - Prospective Studies
KW - Ritonavir/therapeutic use
KW - Viral Load
U2 - 10.1046/j.1365-2796.1999.00615.x
DO - 10.1046/j.1365-2796.1999.00615.x
M3 - SCORING: Journal article
C2 - 10620100
VL - 246
SP - 567
EP - 575
JO - J INTERN MED
JF - J INTERN MED
SN - 0954-6820
IS - 6
ER -