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

Fecha de publicación: 16/06/2019

Autores de IIS La Fe

• Julia Blanco Gonzalez

  Autor

• Iván Castro Hernández

  Autor

• Joaquin Berenguer Lapuerta

  Autor

Participantes ajenos a IIS La Fe

• Resino S
• Navarrete-Muñoz MA
• Pacheco YM
• Santos J
• Vera-Méndez FJ
• Górgolas M
• Jiménez-Sousa MAÁ
• Benito JM
• Rallón N
• CoRIS and the HIV Biobank integrated in the Spanish AIDS Research Network Projec

Grupos

• Investigacion clínica en enfermedades crónicas e Infección por el VIH

  Investigador establecido

  Marta Montero Alonso

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/mm 3 . 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/mm 3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of = 400 CD4 + cells/mm 3 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/mm 3 .

Keywords

• CD4, HIV, IL7RA, SNPs, cART, immune reconstitution