Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis
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.
Citation
Mzinza , D T , Sloan , D J , Jambo , K C , Shani , D , Kamdolozi , M , Wilkinson , K A , Wilkinson , R J , Davies , G R , Heyderman , R S & Mwandumba , H C 2015 , ' Kinetics of Mycobacterium tuberculosis -specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis ' , Tuberculosis , vol. 95 , no. 4 , 1343 , pp. 463-469 . https://doi.org/10.1016/j.tube.2015.05.009
Publication
Tuberculosis
Status
Peer reviewed
ISSN
1472-9792Type
Journal article
Description
This work was supported by funding from the Wellcome Trust (UK) through Fellowships 092773/Z/10/Z (to D.T.M), 086757/Z/08/Z (to D.J.S) and 088696/Z/09/Z (to H.C.M). Core funding from the Wellcome Trust supports the laboratory and office facilities at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
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