Received on March 1, 2006
Accepted on July 18, 2006

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Protease Inhibitor-Associated Dyslipidemia in HIV-Infected Patients Is Strongly Influenced by the APOA5-1131TC Gene Variation

¹ Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain
² Unitat de Recerca de L ípids i Arteriosclerosi, Facultat de Medicina, Universitat Rovira i Virgili, Sant Llorenç, 21, 43201 Reus, Spain. Fax 34-977-75-9322

^* To whom correspondence should be addressed. E-mail: josep.ribalta{at}urv.cat.

Background: Hyperlipidemia associated with the phosphatidylinositol (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 APOA5-1131TC 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 APOA5-1131TC 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 APOA5-1131TC 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/HDLc ratio after 3 years.

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