Objective:To explore the immunogenicity and persistence of hepatitis B vaccine in HIV-infected patients with different CD4 +T cell (CD4) levels, and analyze the influence effect of CD4 levels on immunization response. Methods:A total of 182 HIV-infected patients who participated in a randomized controlled trial of 20 μg and 60 μg hepatitis B vaccination at month 0, 1, and 6 in 2014 by Guangxi Zhuang Atonomous Region CDC and Ningming county CDC were surveyed. Six months later after the first dose and 1 month, 6 months, 1 year, and 3 years later after the full course of the vaccination, 5 ml of the venous blood of the patients was collected, and the anti-HBs was detected by Chemiluminescent Microparticle Immunoassay (CMIA). On the basis of previous studies, this study focused on analyzing the immunogenicity and persistence of hepatitis B vaccine under different CD4 levels.Results:One month later after the whole course of hepatitis B vaccination, the anti-HBs geometric mean concentration (GMC), anti-HBs positive rate (≥10 mIU/ml) and strong positive rate (≥100 mIU/ml) in HIV patients with CD4 <350 cells/μl were 442.50 mIU/ml, 71.05% (27/38) and 44.74% (17/38), respectively, which were significantly lower than those HIV-infected patients with CD4 ≥350 cells/μl [583.90 mIU/ml, 92.13% (117/127) and 77.95% (99/127)] ( P<0.05). After controlling the confounding factors, the probability of being anti-HBs positive induced by hepatitis B vaccine in patients with CD4 <350 cells/μl was 0.14 times higher than in those with CD4≥350 cells/μl (95% CI: 0.03-0.62), and patients with CD4 <350 cells/μl had higher risk of no response. From 6 months to 3 years after the whole course of the vaccination, the anti-HBs GMC (195.00-27.55 mIU/ml vs. 300.10-45.81 mIU/ml), the positive rate (56.67%-36.67% vs. 78.57%- 51.58%) and the strong positive rate (33.33%-6.67% vs.44.64%-15.79%) in patients with CD4 <350 cells/μl gradually declined, lower than the levels in those with CD4 ≥350 cells/μl. Conclusions:HIV-infected patients with CD4 <350 cells/μl have high risk of no response to hepatitis B vaccination and poor immune persistence. It is necessary to strengthen the anti-HBs monitoring in HIV-infected patients, with special attention to those with CD4 <350 cells/μl. When anti-HBs is negative, hepatitis B vaccine should be injected as early as possible.