Objective To investigate the associations of IFNL3/IFNL4 single-nucleotide polymorphisms(SNPs)with the efficacy of highly active antiretroviral therapy(HAART)in patients with HIV-1 infection.Methods Sixty-three adult patients with HIV-1 infection receiving HAART for at least 1 year in the First Affiliated Hospital, Zhejiang University School of Medicine were enrolled.HIV-1 RNA loads in plasma and HIV-1 DNA loads in peripheral blood mononuclear cells(PBMCs),and blood SNPs were detected by quantitative polymerase chain reaction(qPCR).Plasma inflammatory cytokines were examined by magnetic beads method,and the CD4 +T and CD8 +T lymphocyte counts in peripheral blood were measured by flow cytometry.According to response to HAART,the patients were classified as low HIV-1 RNA group(viral load <100 copies/mL)and high HIV-1 RNA group(viral load≥100 copies/mL);according to CD4+T lymphocyte counts,the patients were defined as low CD4+T cell group(<250 cells/μL), and high CD4+T cell group(≥250 cells/μL);according to HIV-1 DNA levels,the patients were divided into low(<100 copies/106cells)and high(≥100 copies/106cells)HIV-1 DNA groups.Results Three candidate SNPs rs368234815,rs8099917 and rs4803223 had significantly different distribution between low and high HIV-1 RNA groups(χ2=0.043,0.047 and 0.032,all P<0.05).The levels of interleukin(IL)-10 were declined in the low HIV-1 RNA group(U=4.00,P<0.05);the levels of IL-13 were decreased in the high HIV-1 RNA group and the high HIV-1 DNA group(U=0.00 and 2.00,both P<0.05);the levels of IL-21 were reduced in the high HIV-1 RNA group and in the low CD4 +T cell group(U=3.00 and 2.00, both P<0.05),the levels of IL-28A were decreased in the high HIV-1 RNA group,the high HIV-1 DNA group,and the low CD4 +T cell group(U=3.00, 0.50 and 3.00,P<0.05 or <0.01).In addition, rs368234815 was associated with IL-21 level(H=6.690,P<0.05),the IL-21 level in rs368234815 ΔG/ΔG [131.88(2.66,174.00)]was higher than that in TT/TT[6.79(2.81,26.48)](P<0.05);rs4803223 was correlated with IFN-γlevel(H=6.690, P<0.05),the IFN-γlevel in GG subtype[62.26(19.45, 96.49)]was higher than that in GA subtype[6.98(2.19, 99.14)](P<0.05).Conclusion The polymorphisms of IFNL3/IFNL4 rs368234815, rs8099917 and rs4803223 are associated with efficacy of HAART and immune-associated cytokines levels in patients with HIV-1 infection.