Pilot Immunology Study

Pilot Immunology Study to Assess ex vivo Regulation of Host Cell-mediated and Humoral Immune Responses during Short Course Anti-TB Treatment of HIV-infected and HIV-non-infected Adults with Initial Episodes of Smear Positive Pulmonary Tuberculosis

Information:

Sponsor - U. S. National Institutes of Health
Principal Investigators – W. Henry Boom, MD, CWRU; Harriet Mayanja-Kizza, MBChB, M.Med., PhD, Uganda-CWRU Research Collaboration

Type of Study Prospective Observational Study
Design Longitudinal or Cross-sectional / Cohort
Project Site Kampala, Uganda
Sample Size 1217 subjects enrolled
Population

Adults, >18 years of age by type of TB disease as follows:

  • Pulmonary tuberculosis: 150 subjects per year (approx 50% HIV-infected)
  • Pleural tuberculosis: 60 subjects per year (approx 50% HIV-infected)
  • No tuberculosis: 300 subjects per year (approx 50% HIV-infected); 80% of these are expected to be TST positive
Study Period October 2002-Present

Goal of Study:

The Pilot Immunology Study provides a framework to assess the regulation and temporal changes in host immune responses during standard short course anti-TB chemotherapy in culture-confirmed pulmonary TB, pleural TB and/or without active TB, HIV-infected or HIV-uninfected individuals. The protocol is intended to assess various immunological markers in subjects with and without TB, in both HIV-infected and uninfected subjects. Depending on the marker of interest, samples are studied at one time point in a cross-sectional manner, or are studied at defined time points in a longitudinal fashion. Immunologic parameters are correlated with clinical and microbiologic changes while subjects are receiving treatment.

Objectives of Study:

  1. Evaluate changes in innate and adaptive immune parameters over time in response to TB treatment in TB patients as measured by ELISA for cytokines and chemokines, by flow cytometry for activation markers on T cells and other immune cells, and by ELISPOT for the frequency of antigen-specific T cells.
  2. Evaluate and compare changes in the innate and adaptive immune parameters mentioned in 1 above between HIV-infected and \x96uninfected TB patients.
  3. Evaluate and compare changes in the innate and adaptive immune parameters mentioned in 1 above between TB patients and MTB infected and uninfected control subjects over time.
  4. Evaluate and compare changes in the innate and adaptive immune parameters mentioned in 1 above between pleural fluid and peripheral blood immune cells in TB patients with pleural disease and effusions.
  5. Evaluate the effect of TB treatment and antiretroviral therapy on immune and virologic parameters in HIV-infected TB patients and HIV-infected control subjects without active TB.
  6. Evaluate whether new methodologies in diagnosis and follow-up of MTB infection and disease can be used to detect MTB infection and disease in HIV-1 infected subjects.