title: Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study.
abstract: BACKGROUND
  The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown.
  
  
  RESULTS
  Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%).
  
  
  CONCLUSIONS
  In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal.
authors.affiliation: The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. stevelawn@yahoo.co.uk
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Sophie V
authors.initials: SV
authors.lastname: Brooks
authors.forename: Katharina
authors.initials: K
authors.lastname: Kranzer
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitelaw
authors.forename: Monica
authors.initials: M
authors.lastname: Vogt
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D000328:Adult; D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D019937:Diagnostic Techniques and Procedures; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis / Q000382:microbiology; D006801:Humans; D008297:Male; D008403:Mass Screening; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D015995:Prevalence; D011446:Prospective Studies; D012293:Rifampin / Q000494:pharmacology*; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology
chemical_list: D012293:Rifampin