title: Effect of tuberculosis preventive therapy on HIV disease progression and survival in HIV-infected adults.
abstract: OBJECTIVE
  To determine whether tuberculosis (TB) preventive therapies alter the rate of disease progression to AIDS or death and to identify significant prognostic factors for HIV disease progression to AIDS.
  
  
  METHODS
  In a randomized placebo-controlled trial in Kampala, Uganda, 2,736 purified protein derivative (PPD)-positive and anergic HIV-infected adults were randomly assigned to four and two regimens, respectively. PPD-positive patients were treated with isoniazid (INH) for 6 months (6H; n = 536), INH plus rifampicin for 3 months (3HR; n = 556), INH plus rifampicin plus pyrazinamide for 3 months (3HRZ; n = 462), or placebo for 6 months (n = 464). Anergic participants were treated with 6H (n = 395) or placebo (n = 323).
  
  
  RESULTS
  During follow-up, 404 cases progressed to AIDS and 577 deaths occurred. The cumulative incidence of the AIDS progression was greater in the anergic cohort compared to the PPD-positive cohort (p < .0001). Among PPD-positive patients, the relative risk of the AIDS progression with INH alone was 0.95 (95% CI 0.68-1.32); with 3HR it was 0.83 (95% CI 0.59-1.17); and with 3HRZ it was 0.76 (95% CI 0.52-1.08), controlling for significant baseline predictors. Among anergic patients, the relative risk of the AIDS progression was 0.81 (95% CI 0.56-1.15). Survival was greater in the PPD-positive cohort compared to the anergic cohort (p = .0001).
  
  
  CONCLUSIONS
  The number of signs or symptoms at baseline and anergic status are associated with increasing morbidity and mortality. Even though the tuberculosis preventive therapies were effective in reducing the incidence of TB for HIV-infected adults, their benefit of delaying HIV disease progression to AIDS was not observed.
authors.affiliation: Division of Biostatistics, Department of Population Health, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. hyun@mcw.edu
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Lim
authors.forename: Alphonse
authors.initials: A
authors.lastname: Okwera
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.forename: Roy D
authors.initials: RD
authors.lastname: Mugerwa
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Whalen
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology / Q000517:prevention & control*; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D016016:Proportional Hazards Models; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*; D014454:Uganda
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin