Safety of and Immune Response to Two Influenza Vaccines in HIV Infected Children and Adolescents

A Phase I/II Randomized Trial of the Safety and Immunogenicity of Cold Adapted Influenza Vaccine (FluMist) in HIV-Infected Children and Adolescents

The purpose of this study is to compare two flu vaccines to determine their safety and ability to stimulate an immune response in HIV infected children and adolescents. This study will also determine how often and how long people who receive a vaccine are able to spread flu vaccine virus to other people.

Influenza virus infections are common among children, particularly during the winter season. The infections are often mild, but more serious cases can cause a number of complications, including respiratory illnesses and bacterial infections. HIV infected children may have an increased risk for developing influenza-related bacterial complications, and influenza infections among this population may lead to more rapid disease progression. The current standard of care for HIV infected children is vaccination with an inactivated influenza vaccine (IAIV). However, IAIV is limited in its ability to stimulate the immune systems of HIV infected children with advanced disease. FluMist, a cold-adapted live attenuated influenza vaccine, is both immunogenic and effective in HIV infected children; unfortunately, FluMist is associated with viral shedding, a period of time when the influenza virus used to produce the vaccine may be transmitted to other people. This study will compare the safety and immunogenicity of IAIV and FluMist in HIV infected children and adolescents. This study will also determine the prevalence and duration of FluMist viral shedding in HIV infected children and adolescents who have received the vaccination.

Participants in this study will be randomly assigned to one of two arms. Arm A participants will receive FluMist; Arm B participants will receive IAIV. A single immunization will occur on Day 0 of the study. Arm A participants will have study visits on Days 3, 14, and 28 or home visits on Days 3 and 14. Participants in Arm B will have a study visit on Day 28. A physical exam will be performed at the initial study visit; blood will be collected at study start and at each visit thereafter. Phone calls will be made to participants throughout the study. All participants will have a final study visit after 6 months.

Inclusion Criteria:

• HIV infected
• Stable highly active antiretroviral therapy (HAART) regimen for at least 16 weeks with no changes in therapy anticipated
• Meet certain CD4 cell count and CD4% requirements
• Viral load of less than 60,000 copies/ml within 60 days prior to study start
• Received inactivated influenza vaccine (IAIV) in at least one of the past 2 years
• Written informed consent of parent or legal guardian
• Availability of parent or legal guardian to be contacted by phone

Exclusion Criteria:

• Immunosuppressive or immunomodulatory therapy within 60 days prior to immunization or immunological testing
• Aspirin or aspirin-containing therapy at the time of vaccination or planned within 42 days after immunization
• History of hypersensitivity to any component of IAIV or FluMist
• History of Guillain-Barre syndrome
• Receipt of any inactivated vaccine within 14 days prior to the study vaccination
• Receipt of any live vaccine within 30 days prior to the study vaccination
• Plans to receive any vaccine within the 30 days following the vaccination
• Receipt of any additional influenza vaccine for the duration of the study
• Prophylactic use of drugs with anti-influenza activity
• Moderate chronic pulmonary disease, obstructive or restrictive
• Cardiopulmonary disease affecting normal childhood activity
• Medically-diagnosed wheezing, bronchodilator use, or steroid use within the past 42 days
• Medical illness associated with suppression of T-cell immunity
• Pregnancy, breast-feeding, or unwillingness to use acceptable methods of contraception for 3 months following vaccination
• Severely immunosuppressed household member
• Receipt of any blood products within 3 months prior to vaccination or expected receipt during the study, including the 6-month follow-up period
• Significant fever or illness within 72 hours prior to vaccination
• Any other condition that would interfere with the study