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

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.