Brief Report: Polymorphisms in TNF-α/TNFR1 Pathway Genes Are Associated With CD4+ T-Cell Recovery in HIV-1-Infected Individuals on Antiretroviral Therapy

Abstract

Background: Antiretroviral therapy (ART) is an important hallmark of HIV-1 treatment, enabling viral load suppression to undetectable levels and CD4+ T-cell recovery. However, some individuals do not recover the CD4+ T-cell count to normal levels, despite viral suppression. We hypothesize that variation in genes involved in extrinsic apoptosis pathways may influence interindividual immune recovery during ART.

Methods: We assessed clinical-epidemiological variables and the allelic/genotypic distribution of functional single nucleotide polymorphisms in genes involved in extrinsic apoptosis pathways (TNFRSF1A: rs1800692 and rs767455; TNFAIP3: rs2270926; NFKBIA: rs8904; and TNF-α: rs1800629) and their relationship with immune recovery in ART-treated (1 year) HIV-1-infected individuals. We enrolled 155 HIV-1-infected individuals, with 102 individuals showing immunological success and 53 with immunological failure.

Results: Through univariate analysis, we observed that the male sex (60.4%, P = 0.002) showed a higher median of age at treatment onset (34.8 years, P = 0.034) and higher time until virological suppression (6 months, P = 0.035), both risk factors for immune failure. Survival analysis revealed that individuals who started ART treatment with CD4+ T-cell count <200 cells/mm3 took a longer time to immunological recovery (median time = 27 months, P = 0.029). ART containing zidovudine also was associated with immune recovery in univariate e multivariate analysis. Variants in TNFRSF1A (rs767455: T and TT; rs1800692-rs767455: T-T combination) and NFKBIA (rs8904: A) genes were associated with immune failure, whereas NFKBIA (rs8904: GA) and TNF-α (rs1800629: GA) were with CD4+ T-cell recovery.

Conclusions: Clinical-epidemiological variants in genes involved in extrinsic apoptosis pathways might influence the CD4+ T-cell immune recovery.