Background: High triglycerides (TG) and low HDL are independent risk factors for coronary heart disease and are frequent metabolic abnormalities seen in HIV-infected patients. Protease inhibitor (PI) therapy has been inconsistently implicated in promoting hypertriglyceridemia and NNRTI appear to have a favorable effect on HDL in some HIV patients. Variation in the ApoA5 gene has been shown to play a role in plasma TG metabolism in the general population and genetic variants of ApoA5 have been proposed to be associated with metabolic toxicities in HIV-positive patients on antiretroviral therapy. The aim of this study was to determine whether carriers of certain ApoA5 variants display a variable response to antiretroviral therapy with respect to plasma levels of TG and HDL.

Methods: We measured metabolic parameters in 263 participants for the –1131T>C polymorphisms of the APOA5 gene. Allele frequencies and genotype distributions were estimated using gene-counting method and Hardy-Weinberg equilibrium (HWE) was tested. χ² test and ANOVA were used to compare categorical and continuous variables across groups. To determine the association between metabolic parameters and antiretroviral therapy for ApoA5 variants, we used ANCOVA.

Results: The relative frequencies of ApoA5 alleles were 0.905 and 0.095 for alleles T and C. The frequencies of ApoA5 genotypes were 81.9, 17.2, and 0.9 % for TT, TC, and CC. These frequencies were consistent with HWE and with those reported in the general population. Baseline characteristics by major and minor variant genotype were not significantly different. Minor allele carriers had a significant TG response to PI therapy compared to those not on PI (310 vs 132, p = 0.011), but not those with the major variant (176 vs 164, p = 0.506). Those with the major variant had a significant increase in HDL in response to NNRTI-based therapy compared to those not on NNRTI (45 vs 39, p = 0.02), but not minor allele carriers (45 vs 45, p = 0.995).

Conclusions: We did observe a significantly different plasma TG and HDL response to antiretroviral therapy between carriers of different ApoA5 variants in HIV-infected patients. Allele-specific response to antiretroviral therapy may explain some of the variability in the development of metabolic complications in HIV-infected persons and could help predict and prevent individual susceptibility to adverse reactions to antiretroviral medications.