Pneumococcal Vaccine and Routine Pediatric Immunizations in HIV-Infected Children Receiving Anti-HIV Drugs

Evaluation of the Immunogenicity of Pneumococcal Conjugate Vaccine and Routine Pediatric Immunizations in HIV-Infected Children Treated With Highly Active Antiretroviral Therapy (HAART)

The purpose of this study is to determine if 2 doses of Pneumococcal Conjugate Vaccine (PCV) followed by 1 dose of Pneumococcal Polysaccharide Vaccine (PPV) in HIV-infected children on anti-HIV therapy is helpful and safe in fighting pneumococcal infections in this group of children. This study will also look at the protection provided by childhood vaccination against measles, pertussis, and hepatitis B virus.

Pneumococcal infections are the most common AIDS-related infection in HIV-infected children. PCV may help reduce the chances of HIV-infected children getting pneumococcal infections. This study will look at whether pneumococcal vaccines are safe and effective in HIV-infected children receiving HAART. It will look at whether HIV-infected children are protected by childhood vaccines received previously and if more doses are safe and improve protection.

Infection by Streptococcus pneumoniae is the most frequent opportunistic infection observed in HIV-infected children. PCVs are immunogenic and efficacious in normal children and offer hope of reducing pneumococcal infections in HIV-infected children. The degree to which children on HAART are protected by prior immunizations and are responsive to new immunizations is still largely undefined. This study is designed to answer whether PCV immunizations are safe and effective. The immune responses to prior immunizations and responsiveness to booster doses of vaccines against measles, pertussis, and hepatitis B virus of children on HAART will also be examined. Answers to these questions will determine whether these children are likely to be protected against these clinically relevant pathogens and whether they should routinely receive booster doses of these vaccines after a period of HAART.

Patients are stratified on the basis of CD4 percentage and age. Patients that previously received a primary hepatitis B vaccine (HBV) series receive an HBV immunization at entry. Other vaccinations may be given (based on age and/or CD4 cell measurement, and immunization status) for PCV at entry and 2 months, and measles-mumps-rubella (MMR) vaccine and PPV at 4 months. Some patients may be administered DTaP at a 6-month visit on the basis of age, previous immunization history, and negative tetanus antibody status. Follow-up visits are done at 8, 12, and 24 months. Blood samples are collected at all clinic visits for assessment of HIV RNA, immune responses against pneumococcus, measles, pertussis, and hepatitis B virus, as well as for laboratory evaluations.

Inclusion Criteria

Patients may be eligible for this study if they:

• Are 2 to 18 years of age.
• Are HIV-infected.
• Have a viral load (amount of HIV in the blood) under 60,000 copies/ml within 30 days of study entry.
• Have been on their current anti-HIV drugs for at least 3 months.
• Have received 4 or more doses of a pertussis vaccine.
• Have received 1 or more doses of measles vaccine unless a CD4 percent or CD4 number ruled out taking the vaccine. (This reflects a change in the CD4 requirement.)
• Expect to be able to complete all study injections and follow-up.
• Have a negative pregnancy test if able to have children and use effective methods of birth control.
• Have parent or guardian's consent if under 18 years of age.
• Have received an approved hepatitis B vaccine series. Not required for study entry, but children who have received this vaccine will be studied.
• (This study was changed to allow patients who became HIV infected after birth, have a viral load between 30,000 and 60,000 copies/ml, and who have been on their current anti-HIV drugs for 3 to 6 months.)

Exclusion Criteria

Patients will not be eligible for this study if they:

• Had a certain CD4 level before beginning anti-HIV drugs and at screening.
• Have received any killed vaccine within 4 weeks, or any live vaccine within 6 weeks, of entering the study.
• Have received pneumococcal vaccines or had a reaction to PPV.
• Have had an allergic reaction to any measles or hepatitis B vaccines, or to other routine childhood immunizations if 13 years of age or less.
• Have any other condition that would make receiving study vaccines inadvisable.
• Are currently on medications that affect the immune system, except for G-CSF and erythropoietin. This includes the equivalent to more than 1 mg/kg/day of prednisone in the 2 weeks preceding study screening. Nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded.
• Have received certain blood products within the previous 6 months.
• Have other diseases of the immune system.
• Have had cancer within 3 months of study screening or are being treated or have been treated for cancer within 3 months of study entry.
• Are pregnant.
• Have any other disease or previous surgery that would interfere with study treatment.
• Are likely to have bleeding disorders.
• Show certain side effects to vaccines at screening.