H1N1 Vaccine at Two Dose Levels in HIV Positive Adults
H1N1 Vaccine at Two Dose Levels in HIV Positive Adults
The purpose of this study is to see how the body reacts to different strengths of the H1N1
 flu shot in persons infected with human immunodeficiency virus (HIV). This study will also
 compare how the CD4 count (cells that help fight disease) affects the body's response to the
 H1N1 flu shot. In this study, 2 strengths of the H1N1 flu shot will be given twice, about 3
 weeks apart. The results of this study will help researchers find out if the different
 strengths of the H1N1 flu shot make the body produce H1N1 antibodies that are better at
 fighting H1N1 flu. About 240 HIV positive subjects, ages 18-64 years, will be asked to take
 part in this study. Study procedures include: blood sampling, physical exams, and use of
 memory aids to record temperature, medications and symptoms. The length of patient
 participation is about 7 months.
Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause
 of febrile respiratory illnesses in Mexico and the United States. It rapidly spread to many
 countries around the world, prompting the World Health Organization (WHO) to declare a
 pandemic on June 11, 2009. The immunosuppression associated with human immunodeficiency virus
 (HIV)-infection has been related to diminished immune responses to vaccination against
 multiple pathogens, including influenza. The widespread use of antiretroviral therapy has
 resulted in a significant decrease in the mortality from HIV/acquired immune deficiency
 syndrome (AIDS) and, as a result, HIV-infected subjects constitute a demographically growing
 subpopulation in the United States. Currently, novel H1N1 vaccines are being evaluated in the
 general population. Researchers propose to evaluate the safety and immunogenicity of the
 novel H1N1 vaccines in HIV-infected subjects, because the data from clinical trials enrolling
 healthy subjects may not apply to immunosuppressed individuals; and an evaluation of the
 immune responses to vaccination against new, pandemic influenza viruses has never been
 performed in HIV-infected subjects. This is a randomized, open label, Phase II study in HIV
 seropositive males and non-pregnant females, aged 18-64 years. This study is designed to
 investigate the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1
 virus vaccine at 2 dose levels. Subjects will be randomized into 2 dose groups, stratified by
 cluster of differentiation (CD4) cell count at enrollment (120 subjects per dose group with
 60 subjects per CD4 cell count stratum, <200/mL or greater than or equal to 200/mL) to
 receive intramuscular (IM) inactivated influenza H1N1 vaccine at 15 mcg (Group 1) or 30 mcg
 (Group 2). The H1N1 vaccine will be administered at Day 0 and Day 21. Following immunization,
 safety will be measured by assessment of adverse events through 21 days following the last
 vaccination (Day 42 for those receiving both doses and Day 21 for those who do not receive
 the second dose), serious adverse events and new-onset chronic medical conditions through 7
 months post first vaccination (Day 201), and reactogenicity to the vaccine for 8 days
 following each vaccination (Day 0-7). A CD4/CD8 panel and viral load will be measured prior
 to first vaccination on Day 0 and at Day 10 post the second vaccination. Immunogenicity
 testing will include hemagglutination inhibition assay (HAI) and neutralizing antibody
 testing on serum obtained on the day of each vaccination (prior to vaccination), on Day 10
 after each vaccination, 21 days following the second vaccination (Day 42) and 6 months after
 the second vaccination (Day 201). The primary objectives of this study are: (safety), to
 assess the safety of the unadjuvanted, inactivated H1N1 vaccine in HIV-1 seropositive adults
 when administered at the 15 mcg or 30 mcg dose and (immunogenicity) to assess the antibody
 response following 1 and 2 doses of inactivated H1N1 vaccine administered intramuscularly at
 the 15 mcg or 30 mcg dose levels in HIV-1 seropositive adults stratified by CD4 count at
 enrollment.
Inclusion Criteria:

 -  Human immunodeficiency virus (HIV) infection defined as documented by an enzyme-linked
 immunosorbent assay (ELISA) and confirmed with a Western blot at any time prior to
 study entry. Serum HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or any Food and
 Drug Administration (FDA) approved antibody test by a method other than ELISA is
 acceptable as an alternative confirmatory test.

 -  Males or non-pregnant females age 18-64, inclusive.

 -  Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral
 oophorectomy or hysterectomy or who are not postmenopausal for greater than or equal
 to 1 year) must agree to practice adequate contraception that may include, but is not
 limited to, abstinence, monogamous relationship with vasectomized partner, barrier
 methods such as condoms, diaphragms, spermicides, intrauterine devices, Depo-Provera
 injections or Implanon implants for at least 30 days following the last vaccination.

 -  Are medically stable, as determined by the Investigator (based on review of health
 status, vital signs, medical history, and targeted physical examination. Vital signs
 must be within normal ranges prior to the first vaccination (heart rate 55-100, blood
 pressure systolic <160, blood pressure diastolic <90).

 -  Receipt of the 2009-2010 seasonal influenza vaccine at least two weeks prior to
 enrollment in this study.

 -  Intend to be available for follow-up visits and phone call access through 7 months
 following receipt of H1N1 vaccine.

 -  Are able to understand and comply with planned study procedures.

 -  Subject receiving regular medical follow-up care for HIV.

 -  Has a documented platelet count of >50,000mm^3 and an absolute neutrophil count (ANC)
 of >500mm^3 within the 3 months prior to study entry.

 -  Provide written informed consent prior to initiation of any study procedures.

 Exclusion Criteria:

 -  Treatment for an opportunistic infection (OI) initiated within 2 weeks prior to
 enrollment, or have symptoms that have not stabilized.

 -  Have a known allergy to eggs or other components of the vaccine (including polymyxin,
 neomycin, and chicken protein).

 -  Women who are pregnant or breastfeeding.

 -  Have a positive urine or serum pregnancy test within 24 hours prior to vaccination.

 -  Use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding
 36 months.

 -  Have a neoplastic disease that will be treated with chemotherapy or radiation, or a
 history of any hematologic malignancy.

 -  Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled
 steroids. For oral or parenteral: prednisone or equivalent (greater than or equal to
 2.0 mg/kg per day or greater than or equal to 20 mg total dose) for more than 2
 consecutive weeks (or 2 weeks total) in the past 3 months. For inhaled steroids: >800
 mcg/day of beclomethasone dipropionate or equivalent within the preceding 6 months.
 (Nasal and topical steroids are allowed.)

 -  Have an uncontrolled major psychiatric diagnosis.

 -  Have a history of receiving immunoglobulin or other blood products within the 3 months
 prior to vaccination in this study.

 -  Received an experimental agent (vaccine, drug, biologic, device, or medication) within
 1 month prior to vaccination in this study or expect to receive an experimental agent
 during this study (prior to the Day 201 follow-up call).

 -  Have received any live licensed vaccines within 4 weeks or inactivated licensed
 vaccines within 2 weeks prior to vaccination in this study or plan receipt of such
 vaccines within 21 days following the second vaccination.

 -  Have an acute or chronic medical condition that, in the opinion of the investigator,
 would render vaccination unsafe, or would interfere with the evaluation of responses.

 -  Have a history of severe reactions following previous immunization with influenza
 virus vaccines.

 -  Have a moderate-severe acute illness, including an oral temperature greater than 100.4
 degrees Fahrenheit, within 72 hours prior to vaccination. (This may result in a
 temporary delay of vaccination).

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

 -  Participated in a novel influenza 2009 H1N1 influenza vaccine study or have history of
 novel 2009 H1N1 influenza infection prior to enrollment.

 -  Have a history of alcohol or drug abuse in the last 3 months.

 -  Plan to travel outside of North America at any time between the first vaccination and
 42 days following the first vaccination.

 -  Have a history of Guillain-Barré Syndrome.

 -  Have any condition that the investigator believes may interfere with successful
 completion of the study.