title: Treatment of active tuberculosis in HIV-coinfected patients: a systematic review and meta-analysis.
abstract: BACKGROUND
  Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse.
  
  
  METHODS
  A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutin-containing regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta-regression was performed using negative binomial regression.
  
  
  RESULTS
  After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1-11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase (n=3352 patients from 35 study arms), thrice-weekly therapy (n=211 patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5-10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8-12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with > or =8 months, or if antiretroviral therapy was not used.
  
  
  CONCLUSIONS
  This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.
authors.affiliation: Montreal Chest Institute, McGill University Health Centre, Montreal, Canada.
authors.forename: Faiz A
authors.initials: FA
authors.lastname: Khan
authors.forename: Jessica
authors.initials: J
authors.lastname: Minion
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
authors.forename: Sarah
authors.initials: S
authors.lastname: Royce
authors.forename: William
authors.initials: W
authors.lastname: Burman
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harries
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012293:Rifampin / Q000627:therapeutic use*; D017211:Treatment Failure; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D012293:Rifampin