title: Interferon-γ release assay in HIV-infected patients with active tuberculosis: impact of antituberculous drugs on host immune response.
abstract: 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.
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sauzullo
authors.forename: Fabio
authors.initials: F
authors.lastname: Mengoni
authors.forename: Angela
authors.initials: A
authors.lastname: Ermocida
authors.forename: Anna P
authors.initials: AP
authors.lastname: Massetti
authors.forename: Claudia
authors.initials: C
authors.lastname: D'Agostino
authors.forename: Gianluca
authors.initials: G
authors.lastname: Russo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Salotti
authors.forename: Mario
authors.initials: M
authors.lastname: Falciano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Mastroianni
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology
chemical_list: D000995:Antitubercular Agents; D007371:Interferon-gamma