title: Tuberculosis resistance-conferring mutations with fitness cost among HIV-positive individuals in Uganda.
abstract: Multidrug-resistant tuberculosis (MDR-TB) is considered to be less transmissible due to the fitness cost associated with drug resistance-conferring mutations in essential genes.
  
  
  
  To test the hypothesis that TB drug resistance-conferring mutations with fitness cost are more frequent among human immunodeficiency virus (HIV) positive than among HIV-negative patients.
  
  
  
  We analysed all strains from the two TB drug resistance surveys conducted in Uganda between 2008 and 2011. Strains phenotypically susceptible to rifampicin and/or isoniazid were assumed to be wild-type; in all other cases, we performed whole-genome sequencing. Mutations at the rpoB531 and katG315 codons were considered without fitness loss, whereas other rpoB codons and non-katG were considered with fitness loss.
  
  
  
  Of the 897 TB patients, 286 (32.1%) were HIV-positive. Mutations with fitness loss in HIV-positive and HIV-negative patients were respectively as follows: non-531 rpoB: 1.03% (n = 3), 0.71% (n = 4) (OR 1.46, 95%CI 0.58-3.68); non-katG: 0.40% (n = 1), 1.0% (n = 6) (OR 0.40, 95%CI 0.07-2.20); rpoB531: 1.49% (n = 4), 0.69% (n = 4) (OR 2.29, 95%CI 0.83-5.77); katG315: 3.86% (n = 11), 2.55% (n = 15) (OR 1.54, 95%CI 0.81-2.90). The odds of mutations with and without fitness cost were higher for patients with a history of previous anti-tuberculosis treatment.
  
  
  
  Our data do not support the hypothesis that resistance-conferring mutations with fitness cost are likely to be often present in HIV-positive individuals.
authors.affiliation: Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium, Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala.
authors.forename: W
authors.initials: W
authors.lastname: Ssengooba
authors.affiliation: National Tuberculosis Reference Laboratory, Ministry of Health, Kampala, Uganda.
authors.forename: D
authors.initials: D
authors.lastname: Lukoye
authors.affiliation: Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: C J
authors.initials: CJ
authors.lastname: Meehan
authors.affiliation: Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala.
authors.forename: D P
authors.initials: DP
authors.lastname: Kateete
authors.affiliation: Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, National Tuberculosis Reference Laboratory, Ministry of Health, Kampala, Uganda.
authors.forename: M L
authors.initials: ML
authors.lastname: Joloba
authors.affiliation: Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium, Division of Infectious Diseases, New York University, New York, NY, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: de Jong
authors.affiliation: Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, KNCV Tuberculosis Foundation, The Hague, The Netherlands.
authors.forename: F G
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: van Leth
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D016680:Genome, Bacterial; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012293:Rifampin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000635:transmission*; D014454:Uganda; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin