Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients

Abstract

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study

“…There is a considerable controversy about adjusting the “p value” after multiple tests on clinical-orientated studies [ 48 , 49 ]. In our study there was a hypothesis supported by theory and previous reports in several infectious diseases [ 10 , 11 ], including HIV infected subjects [ 13 , 14 ] and HIV/HCV coinfected patients [ 15 ], and showing a key role of IL7R polymorphisms in the evolution of patients. Therefore, we were not literally doing a random search of a meaningful result, and our results should not be affected by the fact of carrying out a high number of statistical tests.…”

“…However, OR values were similar to those obtained for individual SNPs. In this regard, we also recently reported that IL7R CTA haplotype (three alleles associated with higher sCD127 levels) was related to lower odds of achieving a SVR [ 15 ].…”

“…Thus, the rs3194051 A allele ancestral would be associated with lower CD127 on CD4+ T-cell, lower frequencies of recent thymic emigrants, and higher plasma sCD127 levels. Furthermore, rs3194051 A allele has been associated with slower CD4+ recovery in HIV infected patients on cART [ 14 ] and lower odds of achieving sustained virological response (SVR) after pegIFNα/ribavirin in HIV/HCV coinfected patients [ 15 ].…”

“…In HIV infection, IL7R polymorphisms have been associated with the decline in the CD4+ cell count in untreated HIV-infected subjects [ 13 ], and CD4+ T-cell recovery in HIV-infected patients on combination antiretroviral therapy (cART) [ 14 ]. In HCV infection, we have recently reported an association between IL7R polymorphisms and virological response to HCV therapy with pegylated interferon alpha plus ribavirin (pegIFNα/ribavirin) [ 15 ]. Thus, IL7R polymorphisms seem to play a crucial role in the physiopathology of these diseases.…”

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design

“…Furthermore, IL7RA polymorphisms are related to autoimmune diseases [ 22 , 23 ] and CD4+ T cell recovery in human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy [ 24 – 26 ]. Among HCV-infected patients, IL7RA polymorphisms have been associated with the response to peg-interferon (IFN)-α/ribavirin therapy against HCV and severe liver fibrosis in HIV/HCV-coinfected patients [ 27 , 28 ].…”