Polymorphisms in TNF-α/TNFR1 pathway genes are associated with CD4+ T cells recovery in HIV-1-infected individuals on antiretroviral therapy.

BACKGROUND Antiretroviral therapy (ART) is an important hallmark of HIV-1 treatment, enabling viral load suppression to undetectable levels and CD4+ T cells 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 clinic-epidemiological variables, and the allelic/genotypic distribution of functional single nucleotide polymorphisms in genes involved in extrinsic apoptosis pathways (TNFRSF1A: rs1800692, rs767455; TNFAIP3: rs2270926; NFKBIA: rs8904; TNF-α: rs1800629) and their relationship with immune recovery in ART treated (one year) HIV-1-infected individuals. We enrolled 155 HIV-1 infected individuals, 102 showing immunological success and 53 with immunological failure. RESULTS Through univariate analysis, we observed that the male sex (60.4%, p=0.002) showed 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 T CD4+ cells count <200 cells/mm3 took a longer time to immunological recovery (median time = 27 months, p=0.029). ART containing zidovudine (AZT) also was associated with immune recovery in univariate e multivariate analysis. Variants in TNFRSF1A (rs767455: T, TT; rs1800692-rs767455: T-T combination) and NFKBIA (rs8904: A) genes associated with immune failure, while NFKBIA (rs8904: GA) and TNF-α (rs1800629: GA), with CD4+ T cells recovery. CONCLUSIONS Clinic-epidemiological and variants in genes involved in extrinsic apoptosis pathways might influence the CD4+ T cells immune recovery.