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

Biomolecules. 2019 Jun 16;9(6):233. doi: 10.3390/biom9060233.

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.

Keywords: CD4; HIV; IL7RA; SNPs; cART; immune reconstitution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / pharmacology*
  • Anti-Retroviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Drug Interactions
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin-7 / genetics*

Substances

  • Anti-Retroviral Agents
  • Receptors, Interleukin-7