Interferon-γ release assay in HIV-infected patients with active tuberculosis: impact of antituberculous drugs on host immune response

• Published in: The New microbiologica Vol. 37; no. 2; pp. 153 - 161
• Main Authors: Sauzullo, Ilaria, Mengoni, Fabio, Ermocida, Angela, Massetti, Anna P, D'Agostino, Claudia, Russo, Gianluca, Salotti, Alessandra, Falciano, Mario, Vullo, Vincenzo, Mastroianni, Claudio M
• Format: Journal Article
• Language: English
• Published: Italy 01.04.2014
• Subjects: Adult; AIDS-Related Opportunistic Infections - diagnosis; AIDS-Related Opportunistic Infections - drug therapy; AIDS-Related Opportunistic Infections - immunology; AIDS-Related Opportunistic Infections - physiopathology; Antitubercular Agents - administration & dosage; Apoptosis - drug effects; Female; Human immunodeficiency virus; Humans; Interferon-gamma - immunology; Interferon-gamma Release Tests - methods; Male; Middle Aged; Mycobacterium; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - physiology; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tuberculosis - diagnosis; Tuberculosis - drug therapy; Tuberculosis - immunology; Tuberculosis - physiopathology
• ISSN: 1121-7138

The objective of the study was to: 1) investigate the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) in HIV-infected patients with active tuberculosis (TB); 2) evaluate the sequential changes in QFT-GIT assay during the treatment response; 3) investigate the direct in vitro effects of antituberculous drugs on both secretion of IFN-g and apoptosis of T cells. Forty-four HIV-patients with active TB were enrolled and tested with QFT-GIT. Thirteen of them were followed longitudinally by QFT-GIT, performed at baseline and six and nine months after TB-treatment onset. For in vitro experiments, cells from healthy donors and HIV-naive subjects were pretreated with four antituberculous-drugs, and then examined for IFN-g secretion and apoptosis of T-cells. The QFT-GIT was positive in 66%, negative in 11.3% and indeterminate in 22.7%. Longitudinal analysis in 13 HIV-TB subjects showed that at therapy completion a reversion to negative response was found only in 38.4% of patients, but in 30.7% the QFT-GIT remained positive. Overall, during the anti-TB treatment no significant decrease in average IFN-g response was observed in these patients (p<0.001). In vitro experiments showed that the four antituberculous- drugs, within the range of therapeutically achievable concentrations, did not exert any down-regulatory effect on IFN-g production and did not have any effect on apoptosis of T cells from HIV naïve subjects. Despite the high rate of indeterminate results, QFT-GIT assay may represent a good tool in the diagnostic workup for active TB in HIV-patients. Although the antituberculous drugs do not have any direct effect on host immune response to mycobacterial antigen, changes in longitudinal IGRA response have been found during in vivo anti-TB treatment.