title: Effects of isoniazid resistance on TB treatment outcomes under programmatic conditions in a high-TB and -HIV setting: a prospective multicentre study.
abstract: The scale and impact of background isoniazid resistance in TB- and HIV-endemic countries requires definition to improve treatment success and guide the scale-up of isoniazid preventive therapy (IPT). We describe the effects of isoniazid resistance on TB treatment outcomes among patients with or without HIV infection in Dar es Salaam, Tanzania.
  
  
  
  A multicentre, prospective observational study was conducted among TB patients commencing WHO-recommended first-line TB treatment. In multivariate analysis we ascertained the relationship between isoniazid resistance at presentation with a composite of poor treatment outcomes (death, failure or default from TB therapy).
  
  
  
  Of 861 patients, 250 (29.0%) were HIV infected and 23 (2.7%) had isoniazid resistance. Seven hundred and ninety-seven (92.6%) of the patients were successfully treated and 25 (2.9%) died. Isoniazid resistance [relative risk (RR) = 6.0; 95% CI = 1.9-18.7; P  <   0.01] and HIV infection with (RR = 2.3; 95% CI = 1.0-5.2; P  =   0.05) or without (RR = 3.1; 95% CI = 1.5-6.2; P  <   0.01) ART were independent predictors of poor treatment outcomes.
  
  
  
  Background isoniazid resistance and HIV infection adversely affected TB treatment outcomes. Early laboratory detection of isoniazid resistance is important for successful TB therapy. Studies on the impact of background isoniazid resistance on the efficacy of isoniazid prophylaxis are recommended.
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.|Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Tumaini J
authors.initials: TJ
authors.lastname: Nagu
authors.affiliation: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.affiliation: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
authors.forename: Mecky I
authors.initials: MI
authors.lastname: Matee
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Maeurer
authors.affiliation: Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
authors.affiliation: Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Mugusi
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011446:Prospective Studies; D012306:Risk; D013636:Tanzania / Q000453:epidemiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid