Hepatitis B Vaccine Responsiveness and Clinical Outcomes in HIV Controllers

Background: Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied. Methods and Findings: In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) $10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n = 44) and treatment-naı̈ve non-controllers (n = 476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n = 284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n = 143) and non-controllers (n = 1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naı̈ve non-controllers (36.6%; P,0.001), but similar to non-controllers on HAART (59.9%; P = 0.549). Factors associated with vaccine response for HIC compared to HAART-naı̈ve non-controllers include HIC status (OR 2.65, 95 % CI 1.23–5.89; P = 0.014), CD4 count at last vaccination (OR 1.28, 1.15–1.45 for every 100 cells/uL; P,0.001), and number of vaccine doses administered (OR 0.56, 0.35–0.88; P = 0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1–1.38 for every 100 cells/uL; P,0.001). The rate of AIDS or deat