Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen

Abstract

Objectives: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study.

Patients and methods: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays.

Results: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274.

Conclusion: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.

Figure 1

Median (interquartile range) evolution in CD4 T cell count from baseline to M6 in patients receiving efavirenz-containing therapy according to the different genotype profiles in the three SNPs. The light gray boxplot represents the baseline CD4 T cell count, while the dark gray boxplot represents the median CD4 T cell count at M6. The horizontal lines represent the median and the lower and upper limits of the boxplot represent 25% percentile and 75% percentile. Mann–Whitney test were used to compare CD4 T cell count from baseline to that of M6.

Figure 2

Median CD4 T cell count evolution from baseline to M6 in patients regarding the different combinations of wild-type homozygous/heterozygous in the three SNP. The light gray boxplot represents the baseline CD4 T cell count, while the dark gray boxplot represents the median CD4 T cell count at M6. The horizontal lines represent the median and the lower and upper limits of the boxplot represent 25% percentile and 75% percentile. Mann–Whitney test were used to compare CD4 T cell count from baseline to that of M6.