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

Abstract

Objective: To determine whether interferon-gamma release assays (IGRAs) improve the identification of HIV-infected individuals who could benefit from latent tuberculosis infection therapy.

Design: Systematic review and meta-analysis.

Methods: We searched multiple databases through May 2010 for studies evaluating the performance of the newest commercial IGRAs (QuantiFERON-TB Gold In-Tube [QFT-GIT] and T-SPOT.TB [TSPOT]) in HIV-infected individuals. We assessed the quality of all studies included in the review, summarized results in prespecified subgroups using forest plots, and where appropriate, calculated pooled estimates using random effects models.

Results: The search identified 37 studies that included 5736 HIV-infected individuals. In three longitudinal studies, the risk of active tuberculosis was higher in HIV-infected individuals with positive versus negative IGRA results. However, the risk difference was not statistically significant in the two studies that reported IGRA results according to manufacturer-recommended criteria. In persons with active tuberculosis (a surrogate reference standard for latent tuberculosis infection), pooled sensitivity estimates were heterogeneous but higher for TSPOT (72%; 95% confidence interval [CI], 62-81%) than for QFT-GIT (61%; 95% CI, 47-75%) in low-/middle-income countries. However, neither IGRA was consistently more sensitive than the tuberculin skin test in head-to-head comparisons. Although TSPOT appeared to be less affected by immunosuppression than QFT-GIT and the tuberculin skin test, overall, differences among the three tests were small or inconclusive.

Conclusions: Current evidence suggests that IGRAs perform similarly to the tuberculin skin test at identifying HIV-infected individuals with latent tuberculosis infection. Given that both tests have modest predictive value and suboptimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistic considerations.

Figure 1. Sensitivity of IGRAs in HIV-infected individuals with confirmed active tuberculosis

The forest plots display the sensitivity estimates obtained from individual studies and pooled estimates derived from random effects modeling. Pooled estimates are shown only for sub-groups in which 4 or more studies were available. Abbreviations: IGRA, interferon-gamma release assay; CI, confidence interval; TSPOT, T-SPOT. TB, QFT-GIT, QuantiFERON-Gold In-tube.

Figure 2. Proportion of indeterminate IGRA results in HIV-infected persons screened for LTBI

The forest plots display the proportion of indeterminate IGRA results obtained from individual studies and pooled estimates derived from random effects modeling. Pooled estimates are shown only for sub-groups in which 4 or more studies were available. Abbreviations: IGRA, interferon-gamma release assay; CI, confidence interval; TSPOT, T-SPOT. TB, QFT-GIT, QuantiFERON-Gold In-tube.

Figure 3. Impact of CD4+ cell count on the proportion of positive IGRA results

The forest plots display the absolute difference in the proportion of positive IGRA results between persons with CD4+ cell count > 200 cells/μl and CD4+ cell count <100 cells/μl obtained from individual studies and pooled estimates derived from random effects modeling. Pooled estimates are shown only for sub-groups in which 4 or more studies were available. Abbreviations: IGRA, interferon-gamma release assay; CI, confidence interval; TSPOT, T-SPOT. TB, QFT-GIT, QuantiFERON-Gold In-tube.

Figure 4. Impact of CD4+ cell count on the proportion of indeterminate IGRA results

The forest plots display the absolute difference in the proportion of indeterminate IGRA results between persons with CD4+ cell count > 200 cells/μl and CD4+ cell count <100 cells/μl obtained from individual studies and pooled estimates derived from random effects modeling. Pooled estimates are shown only for sub-groups in which 4 or more studies were available. Abbreviations: IGRA, interferon-gamma release assay; CI, confidence interval; TSPOT, T-SPOT. TB, QFT-GIT, QuantiFERON-Gold In-tube.