PT  - JOURNAL ARTICLE
AU  - M.X. Rangaka
AU  - H.P. Gideon
AU  - K.A. Wilkinson
AU  - M. Pai
AU  - J. Mwansa-Kambafilwe
AU  - G. Maartens
AU  - J.R. Glynn
AU  - A. Boulle
AU  - K. Fielding
AU  - R. Goliath
AU  - R. Titus
AU  - S. Mathee
AU  - R.J. Wilkinson
TI  - No discriminatory value of interferon release added to smear negative HIV-tuberculosis algorithms
AID  - 10.1183/09031936.00058911
DP  - 2011 Jan 01
TA  - European Respiratory Journal
PG  - erj00589-2011
4099  - http://erj.ersjournals.com/content/early/2011/06/28/09031936.00058911.short
4100  - http://erj.ersjournals.com/content/early/2011/06/28/09031936.00058911.full
AB  - Clinical algorithms for evaluating HIV-infected individuals for TB prior to isoniazid preventive (IPT) perform poorly, and interferon-gamma release assays (IGRA) have moderate accuracy for active TB. It is unclear if, when used as adjunct tests, IGRA add any clinical discriminatory value for active TB diagnosis in the pre-IPT assessment.A cross-sectional evaluation of 779 sputum smear-negative HIV-infected persons established on, or about to commence, combined anti-retroviral therapy (ART) who were screened for TB prior to IPT. Stepwise multivariable logistic regression was used to develop clinical prediction models. Discriminatory ability was assessed by receiver operator characteristic area under the curve (AUC). QuantiFERON Gold In-Tube (QFT) was evaluated.The prevalence of smear-negative TB by culture was 6.4% (95% CI 4.9-8.4%). Used alone, QFT and the TST had comparable performance; the post-test probability of disease based on single negative tests was 3–4%. In a multivariable model, QFT test did not improve the ability of a clinical algorithm that included not being on ART, weight less than 60 kg, no history of prior TB, any one positive TB symptom/sign (cough≥2 weeks) and CD4+ count less than 250 cells/mm3 to discriminate smear negative culture positive and negative TB (72% to 74%, AUC comparison p=0.33). The TST marginally improved the discriminatory ability of the clinical model (to 77%, AUC comparison p=0.04).QFT does not improve the discriminatory ability of current TB screening clinical algorithms used to evaluate HIV-infected individuals for TB ahead of preventive therapy. Evaluation of new TB diagnostics for clinical relevance should follow a multivariable process that goes beyond test accuracy.