T Cell Activation and Cytokine Profile of Tuberculosis and HIV-Positive Individuals during Antituberculous Treatment and Efavirenz-Based Regimens

PLoS One. 2013 Jun 19;8(6):e66095. doi: 10.1371/journal.pone.0066095. Print 2013.

Abstract

Introduction: The profile of immune activation markers in tuberculosis and HIV-infected patients is already known. The impact of simultaneous infections on the immune parameters is still not fully explored.

Methods: We conducted a prospective study to estimate trajectories of activated T cell subsets and the profile of anti- and pro-inflammatory cytokines in a group of HIV-TB individuals, previously naïve for HAART, recruited from a randomized clinical trial during TB treatment and first antiretroviral therapy with efavirenz. Patients were evaluated according to the immunosuppression levels at baseline as group 1 (CD4<200 cells/mm(3)) and group 2 (CD4>200 cells/mm(3)). These parameters were measured at the time of HAART initiation (started about 30 days after the onset of TB treatment) and at the follow-up visits after 30, 60, 90 and 180 days. Trajectories were estimated using least squares estimates of the coefficients of a restricted cubic spline function in time after adjusting for subject effects, bootstrapping it 500 times.

Results: Increase of CD4 T cell counts and suppression of HIV viral load were observed for all patients under HAART and TB treatment. Descendent trajectories were observed for the activated CD8(+)/CD38(+) and CD3(+)/HLA-DR(+) T cell subsets, and for plasma concentration of gamma- interferon (IFN-γ). Except for TNF-α and IL-2 discrete variations were observed for the other cytokines. Differences in the trajectories of these parameters were observed for groups 1 and 2. Higher values of IFN-γ, IL-2, IL-6 and IL-10 were observed for group 1 from the baseline to two months after treatment initiation, whereas reduced levels of TNF-α were observed for this group between 60 and 120 days of HAART.

Conclusion: Independent of the immunosuppression profile at baseline, HIV-TB patients under HAART were able to recover the CD4(+) T cell counts, and control viral replication and immune activation parameters over time.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alkynes
  • Antiretroviral Therapy, Highly Active
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / pharmacology
  • Benzoxazines / administration & dosage*
  • Benzoxazines / pharmacology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cyclopropanes
  • Cytokines / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1 / drug effects
  • Humans
  • Lymphocyte Activation / drug effects
  • Male
  • Mycobacterium / drug effects
  • Prospective Studies
  • Treatment Outcome
  • Tuberculosis / drug therapy*
  • Tuberculosis / immunology
  • Viral Load / drug effects

Substances

  • Alkynes
  • Antitubercular Agents
  • Benzoxazines
  • Cyclopropanes
  • Cytokines
  • efavirenz

Grants and funding

MCT/CNPq/MS-SCITIE-DECIT 25/2006 is acknowledged for providing financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.