IL7RA polymorphisms predict the CD4+ recovery in HIV patients on cART

Abstract

Background: The IL7RA polymorphisms have recently been associated with CD4+ T-cell decline in untreated HIV-infected subjects and CD4+ T-cell recovery in patients on combination antiretroviral therapy (cART). The aim of this study was to evaluate whether IL7RA polymorphisms are associated with CD4+ T-cell recovery in HIV-infected patients on long-term cART.

Study design: We performed a retrospective study in 151 naïve cART patients with severe immunodeficiency (CD4+ counts ≤200 cells/mm(3) ). IL7RA polymorphisms' genotyping was performed using Sequenom's MassARRAY platform. The outcome variable was the time to achieve the first value of CD4+ count ≥500 cells/mm(3) during the follow-up.

Results: Two different trends of CD4+ T-cell recovery were found in Kaplan-Meier analysis. During the first 48 months, 60 of 151 (39·7%) of the patients reached CD4+ T-cell values ≥500 cells/mm(3) , and no differences were observed between IL7RA genotypes. After the first 48 months of follow-up, 27 of 151 (17·8%) of the patients reached CD4+ T-cell values ≥500 cells/mm(3) , with a different pattern of CD4+ recovery depending on IL7RA genotype. Patients with rs10491434 TT genotype and rs6897932 TT genotype were more likely of achieving CD4+ value ≥500 cells/mm(3) than patients with rs10491434 CT/CC genotype (adjusted hazard ratio (aHR) = 3·59; P = 0·005) and patients with rs6897932 CC/CT genotype (aHR = 11·7; P < 0·001).

Conclusions: The IL7RA polymorphisms seem to be associated with CD4+ T-cell recovery in HIV-infected patients who started cART with severe immunodeficiency, in the second phase of CD4+ T-cell recovery after long-term cART.

Keywords: AIDS; IL7RA; antiretroviral therapy; immune system reconstitution; polymorphisms.