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Comparison of an Interferon-g Release Assay to Conventional Tuberculin Skin Testing for the Diagnosis of Latent TB Infection in HIV-infected Individuals in San Francisco
Annie Luetkemeyer*1,2, Annie Luetkemeyer*1,2, E Charlebois1,2, E Charlebois1,2, L Flores2, D Bangsberg2,3, D Bangsberg2,3, S Deeks2, J Martin2, and D Havlir2
1Ctr for AIDS Prevention Studies, Univ of California, San Francisco, US; 2Univ of California, San Francisco and San Francisco Gen Hosp, US; and 3Epidemiology and Prevention Interventions Ctr, Univ of California, San Francisco, US
Background: Latent tuberculosis infection (LTBI) diagnosis
is a priority in HIV-infected individuals, who have a higher rate of
reactivation TB than immunocompetent persons.
Interferon-gamma (IFN-γ) release assays (IGRA) are approved for the diagnosis of LTBI,
but limited data exist regarding their performance in HIV infection.
Methods: Subjects were sampled from the SCOPE and REACH cohorts, 2 San Francisco studies of
chronically HIV-infected adults. Tuberculin skin test (TST) results, performed
using 5 TU of purified protein derivative, were compared to QuantiFERON®-TB Gold In-Tube (QFT) results, an IGRA that measures IFN-γ response to
early
secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10),
and a portion of tuberculosis antigen TB 7.7.
Results: Of 294 participants who had QFT performed and TST placed, 205 (70%) returned for an evaluable TST interpretation. TST was positive (≥5 mm) in 19 of 205 (9.3%), of whom 12 reported prior
positive TST. QFT was positive in 25 of 294 (8.5%), of whom 11 reported prior
positive TST. Positive
QFT results were predicted by prior
positive TST (adjusted OR 9.0, 95%CI 3.3 to 24.9, p <0.001) and birth in a country with high TB incidence (25
cases/100,000) (AOR 7.1, 95%CI 1.9 to 26.7, p
= 0.004). Excluding
indeterminate QFT results (5.1% of all QFT results), concordance between QFT and TST was 89.3% (κ = 0.34, p =
0.007). Discordance
between QFT and TST occurred in 10.7% of subjects. 5.1% of subjects were TST
positive/QFT negative and 5.6% were TST negative/QFT positive; this decreased
to 2.4% and 3.6%, respectively, if all participants with prior positive TST
were excluded. Lower CD4+ cell count was associated with
more indeterminate QFT results; 16% of
subjects with CD4+
counts <100 cells/mm3 had indeterminate QFT results compared with 3.6% with CD4+ counts 100 to 350 cells/mm3, and 3.9% with CD4+ >350 cells/mm3 (p = 0.007). Lower CD4+ count was also associated with a less robust IFN-γ response to TB antigens (ρ = 0.12, p = 0.046) and a weaker IFN-γ response to positive control (ρ 0.31, p <0.001).
Conclusions: Concordance between QFT and TST in HIV-infected individuals
was high and similar to that reported in immunocompetent
persons. Although QFT
alone would miss only a small percentage (2.4%) of those who tested positive
only on TST, simultaneous QFT and TST testing
would maximize LTBI diagnoses. Further investigation of QFT performance at CD4+
cell counts <100 cells/mm3 is needed.
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