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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Variability in the APOA5 gene predisposes patients with HIV, particularly those treated with PI, to severe hyperlipidemia.
Guardiola
Montse
M
Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.
Ferré
Raimon
R
Salazar
Juliana
J
Alonso-Villaverde
Carlos
C
Coll
Blai
B
Parra
Sandra
S
Masana
Lluís
L
Ribalta
Josep
J
D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008137:Longitudinal Studies; D008297:Male
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D017320:HIV Protease Inhibitors; D008055:Lipids