title: Hepatitis B vaccine responsiveness and clinical outcomes in HIV controllers.
abstract: 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.
  
  
  RESULTS
  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-naïve 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-naïve 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-naïve 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 death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0-0.76) versus 0.98 (95% CI 0.74-1.28) for vaccine responders and 0 (95% CI 0-2.22) versus 4.11 (95% CI 3.38-4.96) for non-responders, respectively.
  
  
  CONCLUSIONS
  HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC.
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Infectious Disease Service, San Antonio Military Medical Center, San Antonio, Texas, United States of America.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Okulicz
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Octavio
authors.initials: O
authors.lastname: Mesner
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Infectious Disease Service, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesan
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Infectious Disease Service, San Antonio Military Medical Center, San Antonio, Texas, United States of America.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: O'Bryan
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Infectious Disease Clinic, Naval Medical Center San Diego, San Diego, California, United States of America.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Deiss
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Agan
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D008297:Male; D008889:Military Personnel; D063868:Patient Outcome Assessment; D011446:Prospective Studies; D012307:Risk Factors; D019562:Viral Load; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines