CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

748 Stool Xpert MTB/RIF and Urine LAM for Diagnosing TB in HIV-Infected Kenyan Children Patricia B. Pavlinac 1 ; Lisa M. Cranmer 2 ; Irene N. Njuguna 3 ;Vincent O. Otieno 3 ; Elizabeth Maleche-Obimbo 3 ; John Gatimu 4 ; Julius Oyugi 5 ; Judd L.Walson 1 ; DaltonWamalwa 3 ; Grace C. John-Stewart 1 1 Univ of Washington, Seattle, WA, USA; 2 Emory Univ Sch of Med, Atlanta, GA, USA; 3 Univ of Nairobi, Nairobi, Kenya; 4 Becton, Dickinson and Company, Nairobi, Kenya; 5 Sch of Med, Univ of Nairobi, Nairobi, Kenya Background: Pulmonary tuberculosis (TB) is a leading cause of mortality in HIV-infected children. Challenges in obtaining respiratory samples from children and rapid TB/HIV disease progression prior to obtaining culture results can lead to treatment delays. Rapid diagnostic tools from easily obtained specimens are urgently needed. Methods: HIV-infected, antiretroviral therapy (ART)-naïve children under 12 years hospitalized for acute illness were enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization ART initiation in Kenya. At enrollment, children provided sputum or gastric aspirate (GA), stool, and urine specimens for TB diagnosis with liquid Mycobacterium tuberculosis (MTB) culture, Xpert MTB/RIF (sputum/GA and stool), and urine lateral flow lipoarabinomannan (LAM) testing, respectively. A second sputum/GA sample for culture was obtained within 72 hours of enrollment. We determined the diagnostic performance of stool Xpert and urine LAM (grade ≥1 considered positive) compared to the combined gold standard of sputum/GA culture and Xpert (positive defined as MTB detection in either of the two cultures or sputum/GA Xpert). 95% confidence intervals (CI) were estimated assuming a binomial distribution.

Results: Among 141 HIV-infected children, median age was 22 months (interquartile range [IQR]: 10-50) and median CD4 was 15% (IQR: 9-23%). Nine children (6%) had microbiologically-confirmed pulmonary TB (5 positive by culture and Xpert, 3 by culture alone, and 1 by Xpert-alone). Stool Xpert identified 6 of 9 children with confirmed TB (sensitivity: 67% [95% CI: 30-93%]; positive predictive value: [PPV] 100.0% [54-100%], Table 1) and classified 130 children as negative (specificity: 99% [95%CI: 95-100%]; negative predictive value [NPV]: 98% [95%CI: 94-100%]). Among 114 children with a urine sample, LAM identified 3 of 6 confirmed TB cases (sensitivity: 50% [95%CI: 12-88%]; PPV: 25% [95%CI: 6-57%]) and classified 96 of 108 children without confirmed TB as negative (specificity: 90% [95%CI: 81-94%]; NPV: 97% [95%CI: 91-99%]). Diagnostic accuracy results were similar when using the gold standard of culture-alone (Table 1). Conclusions: Stool Xpert had moderate sensitivity and high specificity, PPV and NPV for MTB detection compared to sputum/GA culture and Xpert. Urine LAM appears to have poorer sensitivity and PPV, but was assessed in fewer children. Stool Xpert may be useful for accelerating a TB diagnosis in HIV-infected children.

749

High Sensitivity of Abbott RealTime MTB and MTB RIF/INH Resistance Assays Carole L. Wallis 1 ; Neeshan Ramdin 1 ; RaquelV.Viana 1 ; NingTang 2 ; HongWang 2 ; Modiehi Rakgokong 3 ; Joshua Kostera 2 ; Gregor Leckie 2 ; EbrahimVariava 4 ; Neil Martinson 5 1 BARC-SA and Lancet Lab, Johannesburg, South Africa; 2 Abbott Molecular, Des Plaines, IL, USA; 3 Perinatal HIV Rsr Unit, Johannesburg, South Africa; 4 Klerksdorp/Tshepong Hosp, Klerksdorp, South Africa; 5 Perinatal HIV Rsr Unit, Diepkloof, South Africa Background: A major obstacle to the effective treatment of individuals with Tuberculosis (TB) disease is the accurate identification of Mycobacterium tuberculosis (MTB) and drug resistant strains. This study evaluated a novel molecular diagnostic test for TB; the Abbott RealTi m e MTB (Abbott) and Abbott RealTi m e MTB RIF/INH Resistance assays (Abbott Resistance). Methods: Of the 100 individuals who provided sputum samples: 17 were diagnosed with rifampicon (Rif) resistant MTB on a non-study Xpert TM MTB/RIF (GeneXpert); 44 were suspected of having drug sensitive TB disease based on the absence of Rif resistance on the non-study Xpert or clinical evaluation, and 39 were healthy controls. 3ml of sputum was collected and the following assays performed: Study Xpert; Abbott (which detects MTB ); Abbott resistance (which detects Rif and isoniazid [INH] resistance targeting rpoB, katG and inhA upper stream promoter regions) and Hain GenoType MTBDRplus assay (Hain). Liquid Culture using the Mycobacterial Growth Indicator Tube (MGIT) system (Becton Dickinson) and indirect DST were the gold standards. Results: Diagnostic sensitivity and specificity between Abbott and MGIT was 100% and 89%, respectively (Table). Five of the 6 MGIT/Abbott discordant samples were also positive by either GeneXpert and/or Hain. For the 32 MGIT positive samples, Rif and INH resistance was evaluated by indirect DST and Abbott Resistance. Discrepancies are outlined in the Table, the sensitivity or resistance on Abbott was confirmed by either HAIN and/or GeneXpert. The rpoB probe4 mutation was responsible for the Rif resistance in one discrepant sample and katG 315T mutation was responsible for the sample with INH resistance detected by both HAIN and Abbott Resistance. For Abbott Resistance, 8 (38%) samples had both Rif and INH resistance and four samples (19%) had INH mono-resistance. Conclusions: The Abbott RealTi m e MTB and Abbott RealTi m e MTB RIF/INH Resistance assays have a high sensitivity and specificity for detection of MTB and the diagnosis of both Rif and INH resistance. The different resistance patterns observed between the genotypic and phenotypic assays may likely be a result of mutations not targeted by the assay. Although this is a small sample size, INH-mono resistance was detected frequently, indicating the need for a genotypic assay that can detect both Rif and INH resistance.

Poster Abstracts

312

CROI 2016