title: Efficacy of a six-month versus a 36-month regimen for prevention of tuberculosis in HIV-infected persons in India: a randomized clinical trial.
abstract: BACKGROUND
  The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown.
  
  
  METHODS
  An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared.
  
  
  RESULTS
  Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100 py (95%CI- 1.4-3.5) and 1.6/100 py (95% CI-0.8-3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8-3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6-4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant.
  
  
  CONCLUSIONS
  Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients. The trial is registered at ClinicalTrials.gov, NCT00351702.
authors.affiliation: National Institute for Research in Tuberculosis Formerly Tuberculosis Research Centre, Indian Council of Medical Research, Chennai, India. doctorsoumya@yahoo.com
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Pradeep Aravindan
authors.initials: PA
authors.lastname: Menon
authors.forename: Narendran
authors.initials: N
authors.lastname: Gopalan
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Perumal
authors.forename: Ramesh Kumar
authors.initials: RK
authors.lastname: Santhanakrishnan
authors.forename: Ranjani
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Ponnuraja
authors.initials: P
authors.lastname: Chinnaiyan
authors.forename: Sheik
authors.initials: S
authors.lastname: Iliayas
authors.forename: Padmapriyadarsini
authors.initials: P
authors.lastname: Chandrasekaran
authors.forename: Pooranaganga Devi
authors.initials: PD
authors.lastname: Navaneethapandian
authors.forename: Thiruvalluvan
authors.initials: T
authors.lastname: Elangovan
authors.forename: Mai Tuyet
authors.initials: MT
authors.lastname: Pho
authors.forename: Fraser
authors.initials: F
authors.lastname: Wares
authors.forename: Narayanan
authors.initials: N
authors.lastname: Paranji Ramaiyengar
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004977:Ethambutol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000401:mortality*; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; D007538:Isoniazid