title: Enhanced diagnosis of HIV-1-associated tuberculosis by relating T-SPOT.TB and CD4 counts.
abstract: The sensitivity of the tuberculin skin test is impaired in HIV-1-infected persons. Enzyme-linked immunospot-based detection of immune sensitisation may be less affected. Furthermore, the quantitative response can be related to the CD4 count, potentially improving specificity for active disease. The T-SPOT.TB assay was performed on HIV-1-infected participants, 85 with active tuberculosis (TB) and 81 healthy patients (non-TB). The ratio of the sum of the 6-kDa early secretory antigenic target and culture filtrate protein 10 response to the CD4 count (spot-forming cell (SFC)/CD4) was calculated. Using the manufacturer's guidelines, active TB was diagnosed with 76% sensitivity and 53% specificity. Using an SFC/CD4 ratio of 0.12, sensitivity (80%) and specificity (62%) improved. The quantitative T-cell response increased with increasing smear-positivity in the active TB group (p = 0.0008). In the non-TB group, the proportion of persons scored positive by T-SPOT.TB assay was lower in the group with a CD4 count of <200 cells·mm(-3) (p = 0.029). The ratio of the summed T-cell response to CD4 count improved the diagnostic accuracy of the T-SPOT.TB assay in HIV-1-infected persons, and a ratio of SFC/CD4 of >0.12 should prompt investigation for active disease. A strong association between the degree of sputum positivity and T-SPOT.TB score was found. The sensitivity of the T-SPOT.TB assay in active disease may be less impaired by advanced immunosuppression.
authors.affiliation: Faculty of Health Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory 7925, Cape Town, South Africa. tolullahoni@doctors.org.uk
authors.forename: T
authors.initials: T
authors.lastname: Oni
authors.forename: J
authors.initials: J
authors.lastname: Patel
authors.forename: H P
authors.initials: HP
authors.lastname: Gideon
authors.forename: R
authors.initials: R
authors.lastname: Seldon
authors.forename: K
authors.initials: K
authors.lastname: Wood
authors.forename: Y
authors.initials: Y
authors.lastname: Hlombe
authors.forename: K A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: M X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: M
authors.initials: M
authors.lastname: Mendelson
authors.forename: R J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis* / Q000821:virology; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D009169:Mycobacterium tuberculosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014376:Tuberculosis / Q000150:complications* / Q000175:diagnosis* / Q000821:virology
chemical_list: D007371:Interferon-gamma