Risk of progression to active tuberculosis for indeterminate interferon-gamma release assay in immunocompromised individuals: a systematic review and meta-analysis.

BACKGROUND: Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). OBJECTIVES: To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI. DATA SOURCES: PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023. STUDY ELIGIBILITY CRITERIA: Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening. PARTICIPANTS: Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON). REFERENCE STANDARD: None. ASSESSMENT OF RISK OF BIAS: A modified version of the Newcastle-Ottawa Scale. METHODS OF DATA SYNTHESIS: Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA. RESULTS: Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I2 = 0%) and 2.94 (95% CI, 1.78-4.85; I2 = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I2 = 13%) and 2.67 (95% CI, 1.24-5.79; I2 = 23%), respectively. DISCUSSION: Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.