title: 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.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi. Electronic address: dmzinza@gmail.com.
authors.forename: David T
authors.initials: DT
authors.lastname: Mzinza
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi; Department of Medicine, College of Medicine, Private Bag 360, Chichiri, Blantyre 3, Malawi; Institute of Infection and Global Health, University of Liverpool, Liverpool L6 1LY, UK. Electronic address: Derek.Sloan@lstmed.ac.uk.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Sloan
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. Electronic address: Kjambo@liverpool.ac.uk.
authors.forename: Kondwani C
authors.initials: KC
authors.lastname: Jambo
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi. Electronic address: dshani@mlw.medcol.mw.
authors.forename: Doris
authors.initials: D
authors.lastname: Shani
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi. Electronic address: mkamdolozi@mlw.medcol.mw.
authors.forename: Mercy
authors.initials: M
authors.lastname: Kamdolozi
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Rondebosch 7701, Cape Town, South Africa; MRC National Institute for Medical Research, London NW7 1AA, UK. Electronic address: Katalin.Wilkinson@uct.ac.za.
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Rondebosch 7701, Cape Town, South Africa; MRC National Institute for Medical Research, London NW7 1AA, UK; Department of Medicine, Imperial College, London SW7 2AZ, UK. Electronic address: Robert.Wilkinson@uct.ac.za.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi; Department of Medicine, College of Medicine, Private Bag 360, Chichiri, Blantyre 3, Malawi; Institute of Infection and Global Health, University of Liverpool, Liverpool L6 1LY, UK. Electronic address: gerrydavies@doctors.org.uk.
authors.forename: Geraint R
authors.initials: GR
authors.lastname: Davies
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi; Department of Medicine, College of Medicine, Private Bag 360, Chichiri, Blantyre 3, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. Electronic address: livrsh@liverpool.ac.uk.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, P.O. Box 30096, Chichiri, Blantyre 3, Malawi; Department of Medicine, College of Medicine, Private Bag 360, Chichiri, Blantyre 3, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. Electronic address: Henry.Mwandumba@lstmed.ac.uk.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Mwandumba
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D058491:Bacterial Load; D002478:Cells, Cultured; D060085:Coinfection; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016014:Linear Models; D016015:Logistic Models; D008295:Malawi; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: Anti-tuberculosis treatment; Antigen-specific immunity; HIV infection; IFN-γ; Mycobacterium tuberculosis; Pulmonary tuberculosis