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Clin Chem. 2006 Oct;52(10):1914-9. Epub 2006 Aug 3.

Protease inhibitor-associated dyslipidemia in HIV-infected patients is strongly influenced by the APOA5-1131T->C gene variation.

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  • 1Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.



Hyperlipidemia associated with the protease inhibitor (PI) component of highly active antiretrovial treatment can lead to accelerated atherosclerosis. The apolipoprotein A-V (APOA5) gene, which affects VLDL production and lipolysis, may play a role in PI-induced hyperlipidemia, particularly in individuals with the APOA5-1131T-->C genotype.


We measured lipoprotein changes in HIV-positive patients (n = 229) who had been followed for 5 years. For statistical analyses, we segregated the patients with respect to PI treatment and APOA5-1131T-->C genotype.


The frequency of the C allele was 0.08, similar to that in the general population. We found a strong effect of the APOA5-1131T-->C genotype among patients receiving PIs. Carriers of the C allele had consistently increased mean (SD) triglyceride concentrations compared with noncarriers after 1 year [2.11 (1.62) vs 3.71 (4.27) mmol/L; P = 0.009], 2 years [2.48 (2.09) vs 4.02 (4.05) mmol/L, P = 0.050], 3 years [2.32 (1.71) vs 4.13 (4.26) mmol/L; P = 0.013], 4 years [2.90 (2.95) vs 5.35 (7.12) mmol/L; P was not significant], and 5 years [4.25 (5.58) vs 9.23 (9.63) mmol/L; P was not significant]. We observed the same effect on total cholesterol concentrations: after 1 year [4.93 (1.31) vs 5.87 (1.66) mmol/L; P = 0.006], 2 years [5.03 (1.12) vs 6.42 (2.48) mmol/L; P = 0.001], 3 years [5.11 (1.17) vs 6.38 (2.43) mmol/L; P = 0.009], 4 years [5.49 (1.71) vs 6.78 (3.03) mmol/L; P was not significant], and 5 years [5.56 (1.75) vs 7.90 (3.60) mmol/L; P was not significant]. HDL cholesterol showed a progressive reduction, leading to a considerably higher cholesterol/HDL cholesterol ratio after 3 years.


Variability in the APOA5 gene predisposes patients with HIV, particularly those treated with PI, to severe hyperlipidemia.

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