Latent Tuberculosis screening using interferon-gamma release assays in an Australian HIV-infected cohort: is routine testing worthwhile?
BACKGROUND
There are limited data from high-income countries on the performance of interferon-gamma release assays in screening for latent tuberculosis infection (LTBI). We analyzed the routine application of the Quantiferon-TB Gold (QFT-G) assay to detect and predict latent and active TB among HIV-infected patients in Australia.


METHODS
A retrospective cohort study included all HIV-infected patients attending the Melbourne Sexual Health Service between March 2003 and February 2011 who were screened for LTBI using QFT-G. Clinical data were analyzed in multivariable models to determine predictors for QFT-G positivity using logistic regression and active TB development using Cox proportional hazards.


RESULTS
Nine hundred seventeen HIV-infected patients had ≥1 QFT-G performed, of whom 884 (96.4%) were negative, 29 (3.2%) positive, and 4 (0.4%) indeterminate. The mean age was 40.9 years and 88% were male, with median follow-up of 26.4 (interquartile range 15.4-30.7) months. Five hundred fifty (63%) were Australian born, whereas 198 (23%) were born in Asia or Africa. QFT-G was positive in 2.0% of Australian-born, 5.3% of overseas-born [odds ratio: 2.6, 95% confidence interval (CI): 1.2 to 5.6, P = 0.017], and 12.7% of African-born patients (odds ratio 7.1, 95% CI: 2.9 to 17.3, P < 0.001). Two cases of culture-positive TB occurred after QFT-G screening in 3.4% of QFT-G-positive and 0.1% of QFT-G-negative patients (adjusted hazard ratio: 42.4, 95% CI: 2.2 to 827, P = 0.013), a rate of 111 (95% CI: 27.8 to 445) per 100,000 person-years.


CONCLUSIONS
In this context, QFT-G has a high negative predictive (99.9%) value with few indeterminate results. A risk stratification approach to LTBI screening, where HIV-infected patients with epidemiological risk factors for TB infection undergo QFT-G testing, might be clinically appropriate and potentially cost effective in similar settings.
*Victorian Infectious Diseases Reference Laboratory, Melbourne Health, North Melbourne, Victoria, Australia; †Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia; ‡Centre for Population Health, Burnet Institute, Melbourne, Victoria, Australia; §Melbourne Sexual Health Centre, Carlton, Victoria, Australia; and ‖Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Joseph S
JS
Doyle
Melanie
M
Bissessor
Justin T
JT
Denholm
Norbert
N
Ryan
Christopher K
CK
Fairley
David E
DE
Leslie
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D055815:Young Adult