Evaluation of Xpert MTB/RIF Assay for the Rapid Identification of TB and Rifampin Resistance in HIV Infected & HIV uninfected Pulmonary TB suspects: ACTG 5295/TBTC 34 AF Luetkemeyer, C Firnhaber, MA Kendall, X Wu, D Benator, GH Mazurek, B Metchock, P Johnson, S Swindells, I Sanne, DV Havlir, B Grinsztejn, D Alland, on behalf of the ACTG A5295/TBTC 34 Study teams
Evaluation of Xpert MTB/RIF Assay for the Rapid Identification of TB and Rifampin Resistance in HIV Infected & HIV uninfected Pulmonary TB suspects: ACTG 5295/TBTC 34. - PowerPoint PPT Presentation
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Evaluation of Xpert MTB/RIF Assay for the Rapid
Identification of TB and Rifampin Resistance in HIV Infected & HIV
AF Luetkemeyer, C Firnhaber, MA Kendall, X Wu, D Benator, GH Mazurek, B Metchock, P Johnson, S Swindells, I Sanne, DV Havlir, B Grinsztejn, D Alland, on behalf of the ACTG A5295/TBTC 34 Study teams
Disclosures
• Instruments, cartridges and research grant support from Cepheid
• Funding from NIH AIDS Clinical Trials Group (ACTG) and the CDC Tuberculosis Trials Consortium (TBTC)
Background• GeneXpert MTB/RIF: automated real
time PCR that diagnoses M. tuberculosis & identifies rifampin resistance in < 2 hours
• Performance in high TB prevalence settings well characterized– Sensitivity of 1 Xpert: AFB+ 98-99% , AFB-
~60-70%– Specificity: 98-99%
• Limited data for use in lower TB prevalence regions and in HIV coinfection
Study Aims • Determine sensitivity and specificity of
Xpert MTB/RIF assay overall and by AFB smear status
• Rifampin resistant 2.8% (3/109) • Rifampin sensitive 91.7% (100/109) • Contaminated or no growth on DST media
5.5% (6/109)
Non Tuberculosis Mycobacterial(NTM)
Growth
9.3% (67/720)• M. avium complex (MAC): 67% (45) US (45), S. Africa (0), Brazil (0)• M. kansasii: 6% (4) US (3), S. Africa (0), Brazil (1)• Other NTM: 27% (18) US (11), S. Africa (3), Brazil (4)
Sensitivity of 1 Xpert
• No significant impact of region on sensitivity in AFB-/TB culture+
Sensitivity (95% CI)
Xpert +/ TB culture +
Overall 85.8% (78.0%, 91.2%)
91/106
AFB+/TB culture +
100% (94.6%, 100%)
67/67
AFB-/TB culture +
61.5% (45.9%, 75.1%)
24/39
Specificity of 1 Xpert
Specificity (95% CI)
Xpert - / TB culture -
All Participants 98.8% (97.6%, 99.4%)
591/598
AFB+ 100% (51.0%, 100 %)
4/4
AFB- 98.8% (97.6%, 99.4%)
587/594
US only 99.3% (98.0%, 99.8%)
441/444
AFB+ 100% (51%, 100%)
4/4
AFB- 99.3% (98.0%, 99.8%)
437/440
• No significant impact of region on specificity
Xpert Performance in HIV infection
• HIV status did not significantly impact sensitivity or specificity
HIV+ Sensitivity (95% CI)
Specificity (95% CI)
AFB+ 100% (84.5,% 100%)
100% (20.7%, 100%)
AFB- 57.9% (36.3%,76.9%)
98.3% (96.1% , 99.3%)
HIV-
AFB+ 100% (92.3%, 100%)
100% (43.9%, 100%)
AFB- 65.0% (43.3%, 81.9%)
99.3% (97.6,% 99.8%)
Xpert in setting of NonTuberculosis Mycobacteria(NTM) Growth
n Xpert TB positive
AFB+/Non tuberculosis
Mycobacterial Culture +
3(all MAC) 0/3
AFB-/Non tuberculosis
Mycobacterial Culture +
641/64
(this specimen with MAC growth)
Discordance between Xpert & Culture
• All discordance occurred in AFB smear negative specimens
• 10 with Xpert TB+/ TB Culture negative:
n 1st Xpert 2nd Xpert TB culture
4 positive positive negative
3 positive negative negative
2 negative positive negative
1 failure positive negative
Xpert TB Negative /TB culture +
• Of the 15 with 1st Xpert TB negative, 2nd Xpert was TB+ in 3 out of 15 – 20% incremental yield of 2nd Xpert test
• In AFB-/TB culture+: – Sensitivity of 2 Xperts: 69.2% (27/39)– Sensitivity of 1 Xpert: 61.5% (24/39)
Rifampin susceptibility
• 3 Rifampin resistant specimens by culture-based DST: Xpert detected 3 out of 3
• Specificity: 98.8% (81/82)• One participant: Xpert RIF resistant /
• Excellent performance for detection of TB including in low prevalence settings – Sensitivity AFB+100%, AFB- 61.5%– Specificity 98.9% overall, 99.3% in low prevalence
• Performance not significantly impacted by region nor HIV status
• Xpert detected 3 of 3 specimens rifampin resistant specimens by culture
• Data support use of Xpert MTB/RIF in low prevalence settings and in HIV infection
Acknowledgements• Study participants• Support from NIH, CDC, & Cepheid • ACTG 5295 Team• Tuberculosis Trials Consortium (TBTC) S34