Primary Outcome Measures:
- Safety: occurrence of vaccine-associated serious adverse events (SAEs). [ Time Frame: Throughout the course of the study. ] [ Designated as safety issue: Yes ]
- Safety: occurrence of solicited local and systemic adverse events (AE)s. [ Time Frame: Within 8 days post vaccination (Day 0-7). ] [ Designated as safety issue: Yes ]
- Immunogenicity: proportion of subjects, stratified by CD4 count, achieving a serum hemagglutination inhibition assay (HAI) antibody titer of 1:40 or greater, against the novel influenza H1N1 2009 virus. [ Time Frame: Blood samples for serum assays will be collected prior to vaccination on Days 0 and 21, at Day 8-12 after each vaccination and on Day 42 (21 days after the second immunization). ] [ Designated as safety issue: No ]
- Immunogenicity: proportion of subjects, stratified by CD4 count, with 4-fold or greater hemagglutination inhibition assay (HAI) antibody titer increases against the novel influenza H1N1 2009 virus. [ Time Frame: Blood samples for serum assays will be collected prior to vaccination on Days 0 and 21, at Day 8-12 after each vaccination and on Day 42 (21 days after the second immunization). ] [ Designated as safety issue: No ]
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 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 US. 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, and 21 days following the second vaccination (Day 42). The primary objectives of this study are: (safety), to assess the safety of the unadjuvanted, inactivated H1N1 vaccine in HIV-1seropositive 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 15mcg or 30mcg dose levels in HIV-1 seropositive adults stratified by CD4 count at enrollment.
Purpose
