IL7RA rs6897932 Polymorphism Is Associated with Better CD4+ T-Cell Recovery in HIV Infected Patients Starting Combination Antiretroviral Therapy

Abstract

Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4+ recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4+ T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4+ T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4+ T-cells count <200 cells/mm3. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4+ T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy–Weinberg equilibrium (p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4+ T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4+ T-cells increase (AMR = 1.19; p = 0.004), and higher CD4+ T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4+ T-cells at the end of follow-up ≥500 CD4+ cells/mm3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini–Hochberg), only the increase of ≥ 400 CD4+ cells/mm3 lost statistical significance (p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4+ T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4+ T-cells count <200 cells/mm3.

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…The CCL3L1‐CCR5 genotypes, polymorphisms in CD14 and TLR4, mitochondrial haplogroup H, and IL18 G variant allele and genotype were associated with enhanced long‐term CD4 + T‐cell recovery in HIV‐1‐infected patients on suppressive ART. The IL‐7 receptor subunit alpha (IL7RA) rs6897932 CT/TT genotype was related to a faster and better CD4 + T‐cells recovery compared to that of the CC genotype; a potential mechanism is that signal transduction and proliferation in response to IL‐7 was is substantially higher in the "TT" genotype compared to that in the "CC" genotype in HIV‐infected individuals . A study by Greenblatt et al.…”

“…a potential mechanism is that signal transduction and proliferation in response to IL-7 was is substantially higher in the "TT" genotype compared to that in the "CC" genotype in HIV-infected individuals. [187][188][189] A study by Greenblatt et al showed that 41 genes harbored variations that were independently predictive of CD4 recovery. Many of these genes are associated with the cell cycle, apoptosis, lymphocyte migration, or CD4 + T-cell homeostasis.…”

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches

“…They include low baseline antibody responses to Cryptococcus spp., e.g., decreased levels of total plasma IgM and specific antifungal IgM (GXM-IgM or β-glucanbinding IgM) [28], and a lack of pro-inflammatory cytokines in the serum, or CSF, as described below. Genetic factors, such as single nucleotide polymorphism Interleukin 7 receptor subunit alpha (IL7RA), may affect predisposition in the development of IRIS [29]. Allelic polymorphisms (e.g., in CYP2C19 gene) may be considered as patient-specific risk factors affecting fungicidal drug activities, toxicity, and the level of inflammation (e.g., C-reactive protein or albumin levels) [30].…”

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches

“…[81,88]. Recent genetic studies revealed that the T allele homozygosity at rs6897932 of the L-7R gene (encodes CD127) links to a faster CD4+ T cell recovery after ART initiation, as opposed to CC genotypes in HIV-infected individuals [29,89].…”

“…Unmasking CM-IRIS may include neurological symptoms driven by high intracranial pressure and pathways proposed as potential baseline biomarkers, as described below [28]. Genetic factors, such as single nucleotide polymorphism Interleukin 7 receptor subunit alpha (IL7RA) may affect predisposition to developing of IRIS [29]. Allelic polymorphisms (e.g.…”