Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths

• Qualitative Seroresponsiveness to Hepatitis B Surface Antigen [ Time Frame: Week (Wk) 28 (One month after the second immunization) ] [ Designated as safety issue: No ]

  Seroresponsiveness to Hepatitis B Surface Antigen is defined as follows:

  Responder: serum antibody level is greater than or equal to 10 mIU/mL. Non-responder: serum antibody level is less than 10 mIU/mL.

  
  
• Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix (Number of Participants With >=1 Adverse Event (AE)) [ Time Frame: Week 12, Week 24, Week 28, Week 76 ] [ Designated as safety issue: Yes ]
  Frequency Distribution of AEs by Study Arm and Preferred Term. The safety and tolerability of each vaccine was assessed by measuring reactogenicity. The reactions were coded as "Any" vs. "None". In summarizing the distribution of AEs, the number of subjects with at least one event by preferred term and study arm were reported.
  
  
• Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix: Serious Adverse Events (SAE)(Number of Subjects With >= 1 SAE) [ Time Frame: Week 12, Week 24, Week 28, Week 76 ] [ Designated as safety issue: Yes ]
  Frequency Distribution of SAE by Study Arm and Preferred Term. The safety and tolerability of each vaccine was assessed by measuring reactogenicity. The reactions were coded as "Any" vs. "None". The number of participants with at least one SAE is reported.
  
  

• Quantitative Vaccine Response [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  The Log10 titer was used as the quantitative vaccine response.
  
  
• Unadjusted Relationship of Hepatitis B Vaccine Response (Log10 Titer) and Potential Impact Factors Among Subjects Whose Week 28 Antibody Results Are Within Week 28 Visit Window. [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  The Log10 titer at Week 28 was used as the quantitative continuous vaccine response.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen (Binary); Predictor: STUDY ARM. [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Study arm was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SITE EFFECT [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B Surface Antigen is defined as a "Responder" if serum antibody level is >= 10 mIU/mL and a "Non- Responder" if a serum a'body level is < 10 mIU/mL. Site effect was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B)Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Age was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: GENDER [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum a'body level is < 10 mIU/mL. Gender was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: HISPANIC ETHNICITY [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Hispanic ethnicity was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: RACE [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Race was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR FEMALES [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Tanner stage by gender was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR MALES [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Tanner stage by gender was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: BMI at Baseline [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. BMI at baseline was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED CIGARETTES [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever smoked cigarettes was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SEXUAL IDENTITY [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Sexual identity was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE AT WHICH SUBJECT FIRST HAD SEX (NOT FORCED) [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Age of participants' first unforced sexual encounter was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME SEX PARTNERS [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Total number of lifetime sex partners was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME MALE SEX PARTNERS [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Total number of lifetime male sex partners was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME FEMALE SEX PARTNERS [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Total number of lifetime female sex partners was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER DRANK ALCOHOL [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever drank alcohol was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED MARIJUANA [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever smoked marijuana was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER USED DRUGS NOT PRESCRIBE [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever used drugs not prescribed was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.
  
  
• Immunogenicity to Hep B 18 Months After First Immunization [ Time Frame: Week 76 ] [ Designated as safety issue: No ]
  Persistence of protective antibody response was measured by presence or absence of 10 mIU/ml HepB surface antibody and geometric mean titer of the same antibody at Week 76
  
  
• Immunogenicity to Hep A in the Twinrix Arm: One Month Post 2nd Vaccination [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Hepatitis A antibody response in those subjects in the combined vaccine arm (Twinrix) at 1 month after the 2nd vaccination. Immunogenicity to Hepatitis is given as a positive or negative response. If the Hepatitis A serology was reactive, then the participant was considered to have a positive response; if the Hepatitis A serology was non-reactive, then the participant was considered to have a negative response.
  
  
• Immunogenicity to Hep A in Twinrix Arm: Twelve Months Post 2nd Vaccination [ Time Frame: Week 76 ] [ Designated as safety issue: No ]
  Hepatitis A antibody response in those subjects in the combined vaccine arm (Twinrix) at 12 months after the 2nd vaccination. Immunogenicity to Hepatitis is given as a positive or negative response.
  
  
• Immunogenicity to Hep A in Twinrix Arm: Overall Response (1-month or 12-month After 2nd Vaccination) [ Time Frame: Week 28 and Week 76 ] [ Designated as safety issue: No ]
  Hepatitis A antibody response in those subjects in the combined vaccine arm (Twinrix) at two time points: 1 and 12 months after the 2nd vaccination. Immunogenicity to Hepatitis is given as a positive or negative response.
  
  
• As Treated Analysis - Adequate Antibody Response to Hep B Surface Antigen [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  The subject was considered seroresponsive to Hepatitis B Surface Antigen if the serum antibody level was greater than or equal to 10 mIU/mL. Those who received only a single vaccination, whose second vaccination was outside of the specified time window, or other cases of protocol violations were excluded from the analysis.
  
  
• Assessment of Youth Understanding of Vaccine Trial and Informed Consent [ Time Frame: Screening ] [ Designated as safety issue: No ]
  Assessment of understanding was measured by a questionnaire containing six questions. The summary score is the sum of correct answers from six questions.
  
  

Hepatitis B (HBV) prophylactic immunization has been recommended for at-risk adolescents for more than 10 years although universal coverage has not been achieved. Vaccine response in healthy adolescents has generally been reported to be excellent. But, data from the study Reaching for Excellence in Adolescent Care and Health (REACH) that studied HIV-negative adolescents who were at-risk of acquiring Hepatitis B infection through sexual or needle sharing behaviors has demonstrated a much lower than expected vaccine response rate in this population using standard vaccine dosing. Some data suggest that factors such as gender or body mass index might be responsible for the differences in response to the vaccine observed in individuals. The reason for the diminished vaccine response in this population is unclear. If in fact, Hepatitis B vaccine response is diminished in this population, then efforts to determine correlates of response and to improve the response are warranted. The proposed trial will evaluate 2 licensed vaccine products given in a two-dose schedule in youth at risk for hepatitis B and HIV infection to evaluate immunogenicity of the products in this population, barriers to vaccine delivery, and factors which predict a diminished immune response.

Since these youths are also potential candidates for future HIV vaccine trials, participation in such trials will require ability to understand and willingness to volunteer for such trials, ability to return for multiple vaccinations and blood draws to assess vaccine response, and willingness to participate in HIV prevention education. A hepatitis B vaccine trial will provide a licensed vaccine to youth in whom the vaccine is indicated and will allow preliminary assessment of youth's willingness to participate in a vaccine trial that involves blood draws for immunologic assessment.

Tools that will be necessary for HIV vaccine trials in youth include a youth-friendly simplified vaccine trial education component with a required written test for the participant, a standardized risk reduction education program, and a computer-assisted assessment of youth behaviors. These tools can be finalized and field tested in youth participating in the hepatitis B vaccine trial without promoting a false sense of protection from HIV. Secondary objectives of this trial will include assessment of a number of ancillary tools crucial for future HIV vaccine trials. This Hepatitis B vaccine trial will also serve as a HIV vaccine preparedness trial for youth at risk for both Hepatitis B and HIV.

Design: This is a phase II, randomized, single-blinded trial of two hepatitis B immunization regimens in 150 HIV-negative, hepatitis B core antibody, hepatitis B surface antigen and surface antibody negative youth. Vaccinations will be given in a two-dose regimen at 0 and six months (75 subjects in each arm) and the primary outcome will be seroresponsiveness one month after the 6-month dose. Safety and tolerability will also be assessed.