Safety of and Immune Response to an H1N1 Influenza Virus Vaccine in HIV Infected Children and Youth
Safety of and Immune Response to an H1N1 Influenza Virus Vaccine in HIV Infected Children and Youth
Children and people infected with HIV are particularly susceptible to influenza infections.
 This study testED the safety and effectiveness of a vaccine for the new H1N1 influenza virus
 in children and youth infected with HIV.
The new H1N1 influenza virus seen in 2009 has been designated a pandemic by the World Health
 Organization, due to the sustained community outbreaks seen in the United States and Mexico.
 Based on preliminary data, it appears children and young adults were particularly at risk of
 the H1N1 virus. People infected with HIV were also more susceptible to severe influenza
 infections than those who are uninfected. Children with HIV infection, then, have a
 compounded risk of H1N1 infection. Higher doses of influenza vaccines are associated with the
 development of higher levels of serum antibodies, which are needed to resist infection.
 Higher vaccine doses can be used to improve vaccine effectiveness in at-risk populations.
 This study tested the safety and immune response of HIV infected children and youth to a high
 dose of a vaccine for the new H1N1 influenza virus.

 Participation in this study lasted 7 months and had two steps. The first step involved
 receiving the first dose of H1N1 virus vaccine, and the second step, occurring 21 days later,
 involved receiving the second dose of vaccine. Each dose of vaccine was delivered via two
 intramuscular shots (four total injections). After receiving each dose of the vaccine,
 participants were given a diary to record any symptoms or reactions. Participants were
 stratified into three groups by age, including 4 to 9 years, 9 to 18 years, and 18 to 25
 years.

 Participants completed five scheduled visits, taking place at screening, study entry, Days 21
 and 31, and after 7 months. Measurements taken on these visits included a medical history,
 physical and neurological exams, a blood draw, and, when applicable, a pregnancy test. In
 addition to these visits, participants received up to three additional phone calls or visits
 occurring 2 and 10 days after the first dose of vaccine and 2 days after the second dose of
 vaccine to check for reactions to the vaccine.
Inclusion Criteria for Step I:

 -  HIV infected

 -  HIV-1 was perinatally acquired, in the opinion of the investigator

 -  Participants receiving antiretrovirals (ARVs) must have been receiving a stable
 regimen for 90 days prior to entry with no intention to modify their regimen within 60
 days following study entry

 -  Participants not receiving ARVs at entry must not have received ARVs within 90 days
 prior to entry and must NOT plan to initiate ARVs within 60 days following study entry

 -  Ability to complete all study immunizations and evaluations, in the opinion of the
 investigator

 -  Agrees to use contraception, if necessary

 -  Documented platelet count of more than 50,000 per mm3 and an absolute neutrophil count
 (ANC) of more than 500 per mm3 within the 30 days prior to study entry

 -  Youth of legal age (from 18 to 25 years of age), parent or legal guardian, or
 participants who are emancipated minors must provide informed consent

 Inclusion Criteria for Step II:

 -  Received the first dose of Influenza A (H1N1) 2009 monovalent vaccine at least 21 days
 ago

 -  Documented platelet count of more than 50,000 per mm3 and an ANC of more than 500 per
 mm3 within the 30 days prior to Step II entry

 -  If a woman became pregnant after Dose #1, she must be at more than 14 weeks of
 gestation and have her obstetrician's permission to receive the vaccine

 Exclusion Criteria for Step I:

 -  Pregnancy

 -  Known allergy to egg protein (egg or egg product) or other components in the vaccines
 (these may include, but are not limited to: neomycin and polymyxin)

 -  History, in the opinion of the site investigator, of severe reactions following
 previous immunization with seasonal influenza vaccines that would contraindicate
 receipt of any influenza vaccine.

 -  History of probable or proven pandemic 2009 Influenza A (H1N1) infection prior to
 study entry

 -  Has received any live licensed vaccine within 4 weeks or inactivated licensed vaccine
 within 2 weeks prior to study entry

 -  Has received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or
 medication) within 4 weeks prior to study entry or expects to receive another
 nonlicensed agent during the course of the study

 -  Has an acute illness or a documented temperature greater than or equal to 100.0
 degrees Fahrenheit within 24 hours prior to study entry

 -  Use of anti-cancer chemotherapy or radiation therapy within the 36 months preceding
 study entry or has immunosuppression as a result of an underlying illness or treatment
 (other than HIV-1 infection)

 -  Has an active neoplastic disease

 -  Long-term use of glucocorticoids, including oral or parenteral prednisone or
 equivalent (at least 2 mg/kg per day or at least 20 mg total dose) for more than 2
 weeks in the past 6 months or high-dose inhaled steroids (more than 800 mcg/day of
 beclomethasone dipropionate or equivalent) within the preceding 6 months. Nasal and
 topical steroids are allowed.

 -  Has received immunoglobulin or other blood products within the 3 months prior to study
 entry

 -  History of Guillain-Barre syndrome in the subject or subject's family, including
 parents, siblings, half-siblings, and children

 -  Onset of a neurological disorder including (but not limited to) absent ankle and
 patellar deep tendon reflexes in both legs (all four absent) within the past 6 months

 -  Disproportionate loss of strength in lower extremity or extremities compared to the
 upper extremities within the past 6 months

 -  Has any condition that would, in the opinion of the site investigator, place the
 participant at an unacceptable risk of injury or render the participant unable to meet
 the requirements of the protocol

 Exclusion Criteria for Step II:

 -  Has received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or
 medication), other than from participation in this study, since Dose #1 or expects to
 receive another nonlicensed agent before the end of the study

 -  Use of anti-cancer chemotherapy or radiation therapy since Dose #1, new diagnosis of
 an active malignancy, or is immunosuppressed as a result of an underlying illness
 (other than HIV-1 infection) or treatment.

 -  Use of glucocorticoids, including oral or parenteral steroids (at least 2 mg/kg per
 day or at least 20 mg total dose) for more than 2 weeks since vaccine Dose #1 or
 high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or
 equivalent) since Dose #1 (nasal and topical steroids are allowed)

 -  Has received immunoglobulin or other blood products since Dose #1

 -  Any Grade 3 toxicity or adverse event (AE) experienced by a participant, unless the
 investigator has received protocol team approval

 -  Any Grade 4 toxicity or AE (other than injection site reaction or fever) that is
 definitely, probably or possibly related to study vaccine

 -  Any Grade 4 injection site reactions or fever experienced by a participant, unless the
 investigator has received protocol team approval

 -  Any Grade 4 AEs that are definitely not or probably not related to study vaccine,
 unless the investigator has received protocol team approval

 -  New occurrence or new awareness of Guillain-Barre syndrome in the participant or
 participant's family (parents, siblings, half-siblings, or children) since Dose #1

 -  New onset of a neurological disorder including (but not limited to) absent ankle and
 patellar deep tendon reflexes in both legs (all four absent) since Dose #1

 -  Disproportionate loss of strength in lower extremity or extremities compared to the
 upper extremities (not thought to be related to pregnancy) since Dose #1

 -  Documented infection with 2009 Influenza A (H1N1) since Dose #1

 -  Refusal of further vaccination by participant, parent, or guardian

 -  Development of any new disease that the investigator judges to be clinically
 significant or clinically significant findings since Dose #1 that, in the
 investigator's opinion, would compromise the safety of the subject

 -  Withdrawal of consent. Consent may be withdrawn at any time and for any reason,
 without penalty.