Abstract： Objective To investigate the effect of highly active antiretroviral therapy (HAART) on human immunodeficiency virus type-1 ( HIV-1 ) antigen specific cytotoxic T lymphocyte (CTL) immune responses. Methods Peripheral blood mononuclear cells (PBMCs) were collected from 38 HIV-1 infected individuals receiving HAART ( HAART group) and 31 HIV-1 infected individuals not receiving HAART (non-HAART group), and stimulated with a peptide pool containing 12 overlapping peptides in HIV-1 P24;then the frequency of interferon γ ( IFNγ ) secreting cells were assessed by enzyme-linked immunospot (ELISPOT) method. Difference in HIV-1 antigen specific CTL immune response between non-HAART group and HAART group was analyzed by χ2 and Mann-Whitney U tests. Results Positive response rate of HIV-1 antigen specific CTL immune responses in HAART group ( 65.8%, 24/38 ) was higher than that of non-HAART group (32.3%, 10/31, χ2 = 6. 522, P ＜ 0.05 ). For HIV-1 infected individuals with blood CD4 +T cells ＞ 350/μL, the frequency of HIV-1 antigen specific CTL responses in HAART group was higher than that in non-HAART group (Z = -2. 819, P ＜0.05 ). In the HAART group, those receiving HAART more than 12 months were of higher frequency of HIV-1 antigen specific CTL responses ( Z =-2. 195, P ＜ 0. 05 ). Conclusion HAART especially long-term treatment may enhance HIV-1 specific CTL responses in HIV-1 infected individuals.