Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, L'Hospitalet, Barcelona, Spain.
PLoS One. 2012;7(3):e32482. doi: 10.1371/journal.pone.0032482. Epub 2012 Mar 5.
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.
尽管干扰素-γ释放试验（IGRAs）已广泛应用，但它们在诊断结核病和针对 HIV 感染者进行预防性治疗方面的作用仍不明确。我们进行了一项全面的系统评价，以期为 HIV 感染者的循证实践提供依据。
方法/主要发现：我们检索了 MEDLINE、Cochrane 和 Biomedicine 数据库，以确定 2005 年 1 月至 2011 年 7 月期间发表的评估 QuantiFERON®-TB Gold In-Tube（QFT-GIT）和 T-SPOT®.TB（T-SPOT.TB）在 HIV 感染者中的应用的文章。我们评估了它们对诊断结核病和新发活动性结核病的准确性，以及不确定结果的比例。搜索共确定了 38 项可评估的研究，涵盖了 6514 名 HIV 感染者。QFT-GIT 的结核病合并敏感性和特异性分别为 61%和 72%，T-SPOT.TB 为 65%和 70%。在已检测阳性的患者中（各有一项研究），QFT-GIT 和 T-SPOT.TB 的后续活动性结核病累积发病率分别为 8.3%和 10%，而在已检测阴性的患者中（各有两项研究），QFT-GIT 为 0%，T-SPOT.TB 为 0%。QFT-GIT 和 T-SPOT.TB 的合并不确定率分别为 8.2%和 5.9%。在高负担环境中（QFT-GIT 为 12.0%，T-SPOT.TB 为 7.7%），不确定率高于低-中度负担环境（QFT-GIT 为 3.9%，T-SPOT.TB 为 4.3%）。在 CD4+T 细胞计数<200 的患者中（QFT-GIT 为 11.6%，T-SPOT.TB 为 11.4%），不确定率高于 CD4+T 细胞计数≥200 的患者（QFT-GIT 为 3.1%，T-SPOT.TB 为 7.9%）。
结论/意义：IGRAs 对确认或排除 HIV 感染者活动性结核病的准确性欠佳。虽然其对新发活动性结核病的预测值中等，但 QFT-GIT 阴性提示短期至中期风险非常低。确定与不确定结果相关的因素将有助于优化 IGRAs 在临床实践中的应用，尤其是在 HIV 合并感染率高的资源有限的国家。
