CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

711 THE SENSITIVITY OF QUANTIFERON-TB GOLD PLUS IS NOT AFFECTED BY HIV STATUS

L. Telisinghe 1 , M. Amofa-Sekyi 2 , K. Maluzi 2 , D. Kaluba-Milimo 2 , M. Cheeba-Lengwe 2 , K. Chiwele 2 , B. Kosloff 2 , S. Floyd 3 , S. L. Bailey 3 , H. Ayles 4 1 Univ of Bristol, Bristol, UK, 2 Zambart, Lusaka, Zambia, 3 London Sch of Hygiene and Trop Med, London, UK, 4 London Sch of Hygiene and Trop Med, Lusaka, Zambia Background: Interferon gamma release assays (IGRA) and tuberculin skin tests (TST) have poor sensitivity for latent TB infection (LTBI) among people living with HIV/AIDS (PLHIV). By combining CD4 and CD8 mediated immune responses, the new IGRA, QuantiFERON®-TB Gold Plus (QFT®-Plus; QIAGEN), may perform better among PLHIV. We investigated QFT®-Plus sensitivity for active TB (used as a surrogate for LTBI) in a Zambian TB clinic. Methods: Consecutive smear or Xpert MTB/RIF positive adult (≥18years) pulmonary TB patients were recruited between 06/2015-03/2016. Venous blood was tested with QFT®-Plus. All participants were tested for HIV. Using logistic regression, factors associated with positive QFT®-Plus results were explored. Due to the small number of negative/ indeterminate results, individual factors were adjusted for age alone. Results: Among N=108 patients (median age 32 [interquartile range 27-38] years; 73%male and 63% HIV-positive), there were 90 QFT®-Plus positive, 11 negative and seven indeterminate results; sensitivity 83% (95% confidence interval [CI] 75-90%). There was no difference in sensitivity by HIV-status (HIV-positive 85% [95%CI 75-93%; n=68] and HIV-negative 80% [95%CI 64-91%; n=40]; p=0.59). Among PLHIV, sensitivity was lower when CD4 counts were <100cells/µl (50% [95%CI 16-84%]; n=8) compared with ≥100cells/µl (89% [95%CI 75-96%]; n=44) (p=0.02). In models adjusted for age, CD4 count <100cells/µl (odds ratio [OR] 0.15 [95%CI 0.02-0.96]; p=0.05), and, body mass index <18.5Kg/m2 (OR 0.27 [95%CI 0.08-0.91]; p=0.02), were associated with decreased odds of positive QFT®-Plus results. A study conducted at the same clinic in 2007 using the same methods estimated QuantiFERON®-TB Gold In-Tube (QGIT; QIAGEN) and TST sensitivity in a similar population, allowing QFT®-Plus, QGIT and TST sensitivity to be summarised. The overall QFT®-Plus sensitivity was similar to QGIT and TST, with comparable sensitivities among HIV-uninfected patients (Table). However, QFT®-Plus sensitivity was higher among PLHIV, when compared with QGIT and TST. While point estimates suggest QFT®-Plus sensitivity maybe higher than QGIT sensitivity in PLHIV with CD4 counts <100cell/µl, the small numbers in the stratumwith wide CIs preclude any firm conclusions. Conclusion: Overall QFT®-Plus sensitivity is similar to QGIT and TST, but in contrast to these, sensitivity is not affected by HIV-status. QFT®-Plus improves LTBI diagnosis among PLHIV with implications for the management of LTBI in this population. 712 LOOP-MEDIATED ISOTHERMAL AMPLIFICATION ASSAY TO DIAGNOSE TUBERCULOSIS IN RURAL UGANDA Lydia Nakiyingi 1 , Prossy Nakanwagi 2 , Tifu Agaba 1 , Mark Mugenyi 3 , Frank Mubiru 1 , Moses L. Joloba 4 , Yukari C. Manabe 5 1 Infectious Diseases Inst, Kampala, Uganda, 2 Baylor Coll of Med Children’s Fndn, Kampala, Uganda, 3 Kiboga Hosp, Kiboga, Uganda, 4 Makerere Univ, Kampala, Uganda, 5 The Johns Hopkins Univ, Baltimore, MD, USA Background: In resource-limited settings, smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity especially in HIV co-infection, resulting in undiagnosed TB and high mortality. Various molecular tests have been developed to improve TB diagnosis. The loop-mediated isothermal amplification assay (TB-LAMP test) can be staged with minimal infrastructure and is rapid, low cost and detection is with the naked eye. We assessed feasibility and accuracy of Eiken TB-LAMP test in the diagnosis of TB in a high prevalence TB/ HIV rural setting in Uganda. Methods: From October 2013-February 2014, TB-LAMP was carried out on sputum specimens from presumptive TB adults at a district hospital and two low-level health centers in Kiboga district where smear microscopy is the available routine diagnostic option and power cutoffs are frequent. TB LAMP was performed by a technician who had no prior experience in the technology, after a week of training; a simple roomwithout bio-safety cabinet was used. MTB sputum cultures were used as reference standard. Results: Of the 233 presumptive TB (126 at hospital; 107 at low-level health centers); 113 (48.5%) were HIV-infected; 55%male; median age 40(IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. In hospital setting, TB LAMP sensitivity and specificity were 62.2% (95 CI 44.8-77.5) and 97.8% (95 CI 92.1-99.7) respectively, while in low-level health centers, sensitivity and specificity were 50% (95 CI 34.9-65.1) and 98.4% (95 CI 91.2- 100) respectively. Among HIV-infected participants, TB LAMP overall sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively compared to MTB culture. Similar accuracy indices among HIV-infected individuals were observed on stratification by setting. A summary of TB LAMP accuracy indices stratified by setting, determined using various reference standards are shown in the uploaded table. Conclusion: In this high HIV prevalence rural setting, TB LAMP performs better than conventional smear microscopy in the diagnosis of MTB in both hospital and low-level health facilities, as well as among HIV-infected individuals. TB LAMP can easily be performed following a short training period and in the absence of sophisticated infrastructure and expertise. We recommend use of TB-LAMP test in the diagnosis of TB in rural resource-limited settings including low-level health facilities. 713 WITHDRAWN 714 EXTRAPULMONARY TB AT ART PROGRAMS IN LOWER-INCOME COUNTRIES: DIAGNOSTICS AND OUTCOMES Kathrin Zürcher 1 , Marie Ballif 1 , Sasisopin Kiertiburanakul 2 , Marcel Yotebieng 3 , Beatriz Grinsztejn 4 , Denna Michael 5 , Henri Chenal 6 , Matthias Egger 1 , April C. Pettit 7 , Lukas Fenner 1 1 Inst of Social and Preventive Med, Univ of Bern, Bern, Switzerland, 2 Mahidol Univ, Bangkok, Thailand, 3 The Ohio State Univ, Columbus, OH, USA, 4 Inst Nacional de Infectologia (INI-Fiocruz), Rio de Janeiro, Brazil, 5 Natl Inst for Med Rsr, Kisesa HDSS, Mwanza, Tanzania, United Republic of, 6 CIRBA, Abidjan, Côte d’Ivoire, 7 Vanderbilt Univ, Nashville, TN, USA Background: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults. Methods: We collected patient data from HIV/TB co-infected adults (≥16 years) from antiretroviral (ART) programs participating in the IeDEA network in Africa, Asia/Pacific and Central/South America between 2012 and 2014. We categorized TB as PTB (dominant site) and EPTB only. We used multivariable logistic regression to assess association of 1) clinical factors with EPTB and 2) EPTB with clinical outcomes, adjusted for age, sex, history of TB, CD4 cell counts, considering sites heterogeneity. Results: We analysed 2,751 HIV/TB co-infected adults. The median age was 38 years (interquartile range [IQR] 32-45); 1,129 (41%) were female. Of these, 2,103 (76%) had PTB and 648 (24%) EPTB only (Table). At TB treatment start, patients with EPTB had lower median CD4 cell counts compared to PTB (105 vs. 118 cells/µl). Among EPTB patients, the most frequently involved organs were lymph nodes (25%), pleura (15%), abdomen (11%), and meninges (7%, Table). Available diagnostic tests were less frequently used in EPTB compared to PTB patients (58% vs. 80%), whereas in all other cases diagnosis was made based on clinical symptoms. Among EPTB patients, smear microscopy was the most commonly used diagnostic test (49%), followed by culture (13%), and Xpert (3%). Bacteriologic confirmation (culture, smear, Xpert, other molecular tests) was obtained in 837 (40%) of PTB, but only in 103 (16%) of EPTB cases; with the highest proportions of confirmed cases in lymph nodes (30%), meninges (19%), abdomen (14%), joint/bones (11%), pleura (13%), and others (13%). Among patients with CD4 <50 cells/µL, the risk of EPTB was significantly higher than PTB (adjusted odd ratio [aOR] 1.3, 95% confidence interval [CI] 1.1-1.6). EPTB overall was not associated with higher mortality compared to PTB (aOR 1.0, 95% Cl 0.7-1.6), but meningitis was (aOR 2.1, 95% CI 1.3-3.3). Successful outcomes (cured/treatment completed) were as frequent among EPTB compared to PTB cases (aOR 1.1, 95% Cl 0.8-1.3). Conclusion: Diagnosis of EPTB at ART programs in lower income countries was mainly based on clinical symptoms. Strengthening of diagnostic services is needed to improve clinical management of EPTB, particularly in patients with low CD4 cell counts and severe forms. 715LB LOW-LEVEL M. TB GENOTYPIC HETERORESISTANCE PREDICTS PHENOTYPIC DRUG RESISTANCE John Z. Metcalfe 1 , Elizabeth Streicher 2 , Christopher Allender 3 , Darrin Lemmer 3 , Rebecca Colman 4 , Grant Theron 2 , Rob Warren 2 , David M. Engelthaler 3

Poster and Themed Discussion Abstracts

CROI 2017 312