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.
Highlights
The majority of Human immunodeficiency virus (HIV)-infected individuals on combination antiretroviral therapy achieve undetectable levels of plasma HIV-RNA, recover CD4+ T-cell levels in peripheral blood, and restore many immunological functions [1,2]
We performed a retrospective study in 411 HIV-infected patients starting combination antiretroviral therapy (cART) included in two different cohorts: The majority of patients came from the Spanish acquired immune deficiency syndrome (AIDS) Research Network cohort (CoRIS); the rest of the patients came from the AIDS Research Institute IrsiCaixa-HIVACAT, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (Barcelona, Spain) cohort
The baseline characteristics of patients stratified by Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 genotypes are shown in genotype, while 155 carried the CT/TT genotype
Summary
The majority of HIV-infected individuals on combination antiretroviral therapy (cART) achieve undetectable levels of plasma HIV-RNA, recover CD4+ T-cell levels in peripheral blood, and restore many immunological functions [1,2]. Genetic factors have been related to CD4 T-cell restoration after virological suppression, among them specific mitochondrial haplogroups [12] and polymorphisms in genes encoding cytokines or cytokine receptors [13,14,15]. Taken together, all these factors could potentially be employed to predict impaired CD4 T-cell recovery and avoid clinical complications.
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