BackgroundHIV-infected patients are at risk of hepatitis B virus (HBV) coinfection, however, respond worse to HBV vaccination (HBV-V) than immunocompetent adults. This study aimed to determine the response to reinforced HBV-V in HIV-infected subjects under real-life conditions. MethodsHIV-infected patients followed at a Spanish University Hospital who were seronegative for HBV and who received three double-doses (40 µL) of HBV-V at 0, 1 and 2 months were included. Response to HBV-V was defined as HBV surface antibody concentration of ≥10 IU/L 1–12 months after the last HBV-V dose. ResultsOf 332 patients included in the study, 256 (77.1%) showed response to HBV-V. Median (interquartile range) CD4+/CD8+ ratio among the responders was 0.75 (0.52–1.01) versus 0.61 (0.38–0.84) among the non-responders (p = 0.002). Independent predictors for HBV-V response were: female gender [adjusted odds ratio (AOR): 6.240; 95% confidence interval (95%CI): 1.954–19.925; p = 0.002]; non-smoking [AOR: 2.151; 95%CI: 1.243–3.721; p = 0.006]; a CD4+/CD8+ ratio ≥0.67 [AOR: 2.580; 95%CI: 1.209–5.505; p = 0.014] and baseline HIV-RNA ≤50 copies/mL [AOR: 2.049; 95%CI: 1.098–3.824; p = 0.024]. ConclusionAccelerated administration of three double-doses results in considerable high, however still suboptimal, response rates to HBV-V in HIV-infected patients in the clinical practice. A fourth dose should be considered.