Interferon-γ release assays for the diagnosis of tuberculosis and tuberculosis infection in HIV-infected adults: a systematic review and meta-analysis

Abstract

Background: Despite the widespread use of interferon-γ release assays (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy in HIV-infected patients remains unclear. We conducted a comprehensive systematic review to contribute to the evidence-based practice in HIV-infected people.

Methodology/principal findings: We searched MEDLINE, Cochrane, and Biomedicine databases to identify articles published between January 2005 and July 2011 that assessed QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-SPOT®.TB (T-SPOT.TB) in HIV-infected adults. We assessed their accuracy for the diagnosis of tuberculosis and incident active tuberculosis, and the proportion of indeterminate results. The search identified 38 evaluable studies covering a total of 6514 HIV-infected participants. The pooled sensitivity and specificity for tuberculosis were 61% and 72% for QFT-GIT, and 65% and 70% for T-SPOT.TB. The cumulative incidence of subsequent active tuberculosis was 8.3% for QFT-GIT and 10% for T-SPOT.TB in patients tested positive (one study each), and 0% for QFT-GIT (two studies) and T-SPOT.TB (one study) respectively in those tested negative. Pooled indeterminate rates were 8.2% for QFT-GIT and 5.9% for T-SPOT.TB. Rates were higher in high burden settings (12.0% for QFT-GIT and 7.7% for T-SPOT.TB) than in low-intermediate burden settings (3.9% for QFT-GIT and 4.3% for T-SPOT.TB). They were also higher in patients with CD4(+) T-cell count <200 (11.6% for QFT-GIT and 11.4% for T-SPOT.TB) than in those with CD4(+) T-cell count ≥ 200 (3.1% for QFT-GIT and 7.9% for T-SPOT.TB).

Conclusions/significance: IGRAs have suboptimal accuracy for confirming or ruling out active tuberculosis disease in HIV-infected adults. While their predictive value for incident active tuberculosis is modest, a negative QFT-GIT implies a very low short- to medium-term risk. Identifying the factors associated with indeterminate results will help to optimize the use of IGRAs in clinical practice, particularly in resource-limited countries with a high prevalence of HIV-coinfection.

Figure 1. Flowchart for study selection.

Figure 2

Sensitivity of QuantiFERON-TB Gold In-Tube (A) and T.SPOT.TB (B), in HIV-infected patients with confirmed tuberculosis, stratified for tuberculosis burden setting. Pooled estimates derived from random effects (DerSimonian-Laird) modeling.

Figure 3

Specificity of QuantiFERON-TB Gold In-Tube (A) and T.SPOT.TB (B), in HIV-infected patients with confirmed tuberculosis, stratified for tuberculosis burden setting. Pooled estimates derived from random effects (DerSimonian-Laird) modeling.

Figure 4

Proportion of indeterminate results of QuantiFERON-TB Gold In-Tube (A) and T-SPOT.TB (B) in HIV-infected patients, stratified for tuberculosis burden setting. Pooled estimates derived from random effects (DerSimonian-Laird) modeling.

Figure 5. Comparison of the proportion of indeterminate results between HIV-infected and HIV-uninfected individuals.

Pooled estimates derived from random effects (DerSimonian-Laird) modeling.

Figure 6. Differences in the proportion of indeterminate results of IGRAs by 200 CD4⁺ cell count threshold.

Pooled estimates derived from random effects (DerSimonian-Laird) modeling.