Interferon-Gamma Release Assays for the Diagnosis of Latent ... : JAIDS Journal of Acquired Immune Deficiency Syndromes (original) (raw)

Clinical Science

Interferon-Gamma Release Assays for the Diagnosis of Latent Tuberculosis Infection in HIV-Infected Individuals: A Systematic Review and Meta-Analysis

Cattamanchi, Adithya MD; Smith, Rachel MD; Steingart, Karen R MD, MPH; Metcalfe, John Z MD, MPH; Date, Anand MD, MBBS; Coleman, Courtney MPH; Marston, Barbara J MD; Huang, Laurence MD, MAS; Hopewell, Philip C MD; Pai, Madhukar MD, PhD

From the *Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, CA; †Curry International Tuberculosis Center, University of California, San Francisco, San Francisco, CA; ‡Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, GA; §HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA; and ‖Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada.

Received for publication September 30, 2010; accepted December 10, 2010.

This work was supported in part by UNICEF-UNDP-World Bank-WHO Special Programme for Research and Training in Tropical Diseases (TDR), the Stop TB Partnership's New Diagnostics Working Group, the National Institutes of Health (K23HL094141), and the Canadian Institutes for Health Research (MOP-81362 and MOP-89918).

Presented in part at the World Health Organization Guidelines Meeting on Preventive Therapy and Case Finding for TB in People Living with HIV, Geneva, Switzerland, 2010; the World Health Organization Use of Interferon-γ Release Assays in Tuberculosis Control in Low- and Middle-Income Settings, Geneva, Switzerland, 2010; and the American Thoracic Society International Conference, New Orleans, LA, 2010.

The authors have no conflicts of interest to disclose.

Correspondence to: Madhukar Pai, MD, PhD, Assistant Professor & CIHR New Investigator, McGill University, Department of Epidemiology & Biostatistics, 1020 Pine Avenue West, Montreal, QC H3A 1A2, Canada (e-mail: [email protected]).

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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.