Prevention of Pneumococcal Disease in HIV Infection

A K24 award would afford the candidate the opportunity to attain the following objectives: 1) Short-term Objectives: Determine the epidemiology of Streptococcus pneumoniae infections in HIV-infected patients and establish the optimum clinical conditions necessary to facilitate utilization of an innovative, tailored, immunogenic and safe vaccine. 2) Long-term Objectives: The candidate has become proficient at pulse field gel electrophoresis (PFGE) and computer assisted gel analysis. This award will allow her to increase her current technical ability while realizing her aspiration of performing clinical trials. She will obtain her MPH in Epidemiology at the University of Pittsburgh School of Medicine s Program in Clinical Effectiveness/Evaluation Sciences and the Graduate School of Public Health with a focus on epidemiological methods, design of clinical trials, data management and analyses. The candidate will be able to synthesize her technical expertise in bacterial subtyping with her desire to prevent bacterial disease in high risk populations. S. pneumoniae disease is associated with more deaths than any other vaccine- preventable bacterial pathogen. While the 23-valent pneumococcal polysaccharide vaccine covers the majority of invasive serotypes, this vaccine has inferior immunogenicity in HIV-infected patients with CD4 lymphocyte counts <500/mm3. Although the efficacy of one conjugate vaccine has been demonstrated among healthy infants, no efficacy data are available for high- risk populations. The candidate proposes a three tiered approach to preventing pneumococcal disease in HIV infected patients: 1) Using a regional database of over 2000 patients with invasive S. pneumoniae, the candidate will compare serotypes, antibiograms, and case fatality rates between HIV-infected and uninfected individuals. The effect of viral load, and CD4 count on the incidence of recurrent invasive disease will be assessed. The molecular epidemiology of recurrent disease will be performed by comparing PFGE subtypes with dendrograms of genetic relatedness. The HIV-infected patients she sees in the Pittsburgh Aids Center for Treatment (PACT) clinic will be the subjects for two randomized, double-blind vaccine trials. The effect of viral load and HAART on the immunogenicity of the pneumococcal polysaccharide and conjugate vaccines will be assessed. Pneumococcal antibody concentrations will be analyzed by logistic regression to assess the effect of initial viral load and CD4 lymphocyte count. All patients who exhibit a greater that 3-fold transient rise in HIV-1 RNA levels 2 and 4 weeks postimmunization will be evaluated by Fisher's Exact and McNemar's Tests.