Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

David T. Mzinza, Derek James Sloan, Kondwani C. Jambo, Doris Shani, Mercy Kamdolozi, Katalin A. Wilkinson, Robert J. Wilkinson, Geraint R. Davies, Robert S. Heyderman, Henry C. Mwandumba*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
2 Downloads (Pure)

Abstract

In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.

Original languageEnglish
Article number1343
Pages (from-to)463-469
Number of pages7
JournalTuberculosis
Volume95
Issue number4
Early online date28 May 2015
DOIs
Publication statusPublished - 1 Jul 2015

Keywords

  • Mycobacterium tuberculosis
  • Antigen-specific immunity
  • IFN-γ
  • Pulmonary tuberculosis
  • HIV infection
  • Anti-tuberculosis treatment

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