Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth

A Randomized, Open-Label Trial of Three Hepatitis B Vaccination Schemas in HIV-Positive Youth

Hepatitis B is a contagious virus that can damage a person's liver. It can be prevented by vaccination, but for many HIV-positive people, the vaccines do not help them achieve adequate protection against this virus. In an attempt to improve response to vaccination and achieve protection from hepatitis B, this trial will compare the immune system response to 3 hepatitis B vaccine regimens in HIV-positive adolescents 12 through 24 years of age.

Suboptimal response to hepatitis B vaccination in HIV+ adults and children has been well documented in the literature. Given the importance of preventing hepatitis B virus (HBV) co-infection in HIV+ youth and the poor response rates in this population, this study will attempt to improve the immediate and long-term sero-response rates by undertaking a randomized, open-label trial of three hepatitis B vaccination schemas, as follows:

1. standard adult dosing of HBV-only vaccine: Engerix-B 20 mcg at Entry, Week 4 and Week 24
2. increased adult dosing of HBV-only vaccine: Engerix-B 40 mcg at Entry, Week 4 and Week 24
3. standard adult dosing of combined HBV/hepatitis A virus (HAV) vaccine: Twinrix 720 enzyme immunoassay (EIA) HAV Ag plus 20 mcg HBsAg at Entry, Week 4 and Week 24.

This study will also describe the safety of administration of an increased dose of the hepatitis B vaccine in this population. In general, patients undergoing dialysis who have received the dosing regimen recommended for immunocompromised individuals have tolerated the vaccine series well.

Design: This is a stratified, block-randomized, open-label trial of three hepatitis B vaccination schemas in HIV-infected and HBV-uninfected youth. Once randomized, there will be a total of 6 study visits in a 72 week period. Vaccination will occur at Entry, Week 4 and Week 24. Primary sero-response will be evaluated at Week 28 and sustainability of response will be evaluated at Weeks 48 and 72 for those who achieve a primary antibody response of >= 10 IU/ml. Primary non-responders (antibody response of < 10 IU/ml) will be provided with a booster vaccine using the increased-dose Engerix-B vaccine at Week 48 and evaluated for responsiveness at Week 72.

Inclusion Criteria:

• Documented HIV+
• Age 12 to < 25 years
• History of no or one hepatitis B vaccination
• Not pregnant.
• Females engaging in sexual intercourse must be willing to practice an approved method of birth control throughout the completion of the vaccine phase of the study.

Exclusion Criteria:

• History of > 1 hepatitis B vaccination
• Serologic evidence of past or present hepatitis B infection: anti-hepatitis B surface antigen (HBsAg), HBs-Ag or anti- hepatitis B core antigen (HBcAg)
• Previous allergic reaction to hepatitis A or B vaccinations or to yeast, thimerosal or aluminum.
• Active opportunistic infection or current treatment for known or suspected active serious bacterial infection at the pre-entry exam.

Presence of any known grade >= 3 clinical or laboratory toxicity at the time of pre-entry per toxicity tables.

• Anticipation of long-term corticosteroid therapy or within 3 months preceding study randomization. Use of non-steroidal, anti-inflammatory agents and inhaled or topical corticosteroids are allowed.
• Receipt of any restricted medicine listed in the protocol section 8.1.3 within 3 months preceding randomization.
• Receipt of immune globulin product or plasma product within 6 months preceding randomization
• Receipt of licensed blood product or transfusion or any licensed vaccine within 4 weeks preceding randomization.
• Known or suspected diseases of the immune system, other than HIV, or treatment for a malignancy within 3 months of randomization.
• Other serious, acute or chronic medical or surgical conditions must be approved by the protocol chair.