A pilot study to look at the effect of IL-28B polymorphism on IL-28 expression and immunological recovery among HIV infected individuals following ART

Background: Single nucleotide polymorphism (SNP) of IL-28B at rs12979860 and rs8099917 influences the PEG-IFN treatment in HCV infection. Only few studies report effect of this polymorphism on immunological recovery among HIV-1 infected individuals on ART.

Methods: Forty eight treatment naïve HIV infected individuals were recruited in this study and were followed up after 6-9 months of ART. Whole blood sample was collected before and after 6-9 months of ART. Absolute CD4+&CD8+ and CD4/CD8 ratio were estimated using BD FACS Count flow cytometer. IL-28B Polymorphism was detected by PCR-RFLP. Quantification of IL-28 mRNA expression and IL-28B plasma level were done by Real Time PCR and IL-28B ELISA respectively. HIV-1 viral load was measured using Abbott m2000rt. All the variables were analyzed using MedCalc statistical software.

Results: There was a significant(p= <0.0001) increase in the absolute CD4+ T-cell count, CD4/CD3%, IL-28 mRNA following 6-9 months of ART.There was a significant (p = 0.03) association of CC genotype at rs12979860 with higher CD4+ T-cell count among treatment naïve HIV infected individuals. Immune Reconstitution Inflammatory Syndrome(IRIS) was reported in a patient with the genotype TT at rs12979860 and GG at rs8099917. There is no correlation of IL-28B polymorphism with IL-28mRNA and IL-28B plasma level among treatment naïve HIV infected individuals. Between HIV infected individuals and healthy controls significant difference in IL-28mRNA and no significant difference in IL-28 level was observed. There was positive correlation (p=<0.05,rho= 0.394) between IL-28mRNA and HIV-1 viral load in HIV infected individuals. In particular CT (p=0.0003,rho=0.867) at rs12979860 and GT(p=0.01,rho=0.810) at rs8099917 had a significant positive correlation.

Conclusion: Our study showed significantly higher CD4+ T cells in HIV infected individuals with genotype CC prior to ART and significantly high CD4+ T cells and CD4/CD3% following ART. No association of IL-28B polymorphism with IL-28 mRNA and IL-28B plasma level was observed. The increase in IL-28 mRNA expression and HIV-1 viral load before ART and the significant increase in IL-28 mRNA levels after ART and the decrease in HIV viral load after ART in individuals with CT and GT genotypes is a mystery to be answered by further studies.