This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza virus infections occur commonly in normal children in annual winter-spring epidemics. The resulting illness sometimes consists of mild or inconsequential upper respiratory symptoms, but more significant tracheobronchial involvement is also common. Moreover, bacterial superinfection following influenza is common in children, causing otitis media, sinusitis, and pneumonia. Influenza has an even greater potential to cause bacterial complications in some HIV-infected children, and is more likely to complicate their routine care during epidemic periods. There is also the theoretical possibility that this viral illness will enhance HIV replication by activating CD4+ cells (especially in children with incomplete drug suppression) and thereby will stimulate more rapid HIV disease progression. The current standard of care is to immunize HIV-infected children with an inactivated influenza vaccine (IAIV). The immunogenicity of this vaccine in HIV-infected adults and children with advanced disease is limited, whereas it is more likely to induce a strong response in those with less advanced HIV disease (7,8). The efficacy of IAIV in HIV- infected children has not been established. Cold-adapted live attenuated influenza vaccine (FluMistTM) is immunogenic and effective in HIV-uninfected children (9- 10). In these pediatric studies, influenza-related otitis media was also decreased by FluMistTM. FluMistTM is licensed for children 5 to 17 years of age who are immunocompetent. FluMistTM has been safely administered to a small number (n=24) of HIV-infected children (mean age 4.7 years, range 1.0 to 7.9 years) without advanced disease. Signs and symptoms in HIV-infected children were similar to those seen in uninfected children after one or more doses of FluMistTM within each HIV status group, and there were no vaccine-related serious adverse events. Similar results were obtained from 57 HIV-infected adults without advanced disease who received FluMistTM. Additional safety information in HIV-infected children is desirable. The project aims are: 1) To compare the safety of FluMistTM with IAIV in HIV-infected children and adolescents; 2) To compare the immunogenicity of FluMistTM with IAIV in HIV-infected children and adolescents; 3) To determine prevalence and duration of viral shedding of FluMistTM in HIV-infected vaccinees. Secondary aims are: 1) To correlate immune responses and viral shedding with the immunologic Group of the vaccinee (i.e., defined by nadir and current CD4%); 2) Correlate vaccine responses and baseline antibody titer; 3) Determine responses in each Arm and Group after 6 months as a measure of persistence of antibody responses; 4) Correlate immune responses with CD4+ cell count, CD4%, and plasma HIV-1 RNA concentration at the time of immunization; 5) Determine the frequency, duration, and quantity of viral shedding in recipients of FluMistTM (Arm A) as a function of the Group of the vaccine; 6) Determine the homotypic and heterotypic immune responses in each Arm and Group; 7) Correlate humoral and cellular immune responses; and 8) Correlate viral shedding with humoral and mucosal immun
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