Abstract
SummaryIn 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.
Highlights
Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide
Successful treatment of pulmonary TB is associated with reduction in sputum bacillary load and assessment of sputum by smear microscopy and culture after two months of anti-TB treatment to monitor early microbiological response is recommended by the International Union Against Tuberculosis and Lung Disease (IUATLD) [9]
The proportion of patients who successfully cleared Mycobacterium tuberculosis (Mtb) after 2 months of treatment was similar between the two groups (Day 56 smear conversion, HIVÀ 85% vs. HIVþ 86%, Figure 1B; culture conversion, HIVÀ 68% vs. HIVþ 50%, Figure 1C; OR 0.89 [inter-quartile ranges (IQR) 0.02e32.1], p 1⁄4 0.95). While these findings suggest that clearance of Mtb from sputum very early during anti-TB treatment may be slower in HIV-infected than HIV-uninfected individuals, HIV infection is not associated with failure to clear bacilli as duration of anti-TB treatment increases
Summary
D.T. Mzinza et al / Tuberculosis 95 (2015) 463e469 counts [8] underscores the importance of T cell-mediated adaptive immunity in protection against disease caused by Mtb. Successful treatment of pulmonary TB is associated with reduction in sputum bacillary load and assessment of sputum by smear microscopy and culture after two months of anti-TB treatment to monitor early microbiological response is recommended by the International Union Against Tuberculosis and Lung Disease (IUATLD) [9]. Successful treatment of pulmonary TB is associated with reduction in sputum bacillary load and assessment of sputum by smear microscopy and culture after two months of anti-TB treatment to monitor early microbiological response is recommended by the International Union Against Tuberculosis and Lung Disease (IUATLD) [9] There is need to identify other laboratory parameters specific to TB which could be useful rapid surrogate markers of response during treatment of pulmonary TB irrespective of the patient's HIV infection status
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