title: Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial.
abstract: BACKGROUND
  Mortality rates of HIV-infected patients treated for tuberculosis remain high. This study aimed to assess the effect on mortality of immunotherapy with single-dose SRL172 added to standard antituberculosis chemotherapy in such patients.
  
  
  METHODS
  The double-blind trial enrolled 1229 patients aged 18-60 years, who had never received antiretroviral treatment and who presented with newly diagnosed, sputum-smear-positive pulmonary tuberculosis to referral centres in Lusaka, Zambia, and Karonga, Malawi. Both HIV-positive and HIV-negative patients were enrolled, to avoid stigmatisation. Participants were randomly assigned a single injection of SRL172 or matching placebo within 2 weeks of starting 8 months of antituberculosis chemotherapy and followed up for at least 12 months. The primary endpoint was time to death in the HIV-infected population. Analyses were based on 760 HIV-positive patients after exclusion of 84 patients with errors in storage of the injection, no bacteriological confirmation, or no HIV result.
  
  
  RESULTS
  Of 760 HIV-infected patients, 374 received SRL172 and 386 received placebo. SRL172 did not cause any serious adverse events. The follow-up rate was 88% at 12 months in both groups. Of the HIV-positive patients, 109 (19.5 per 100 person-years) of 372 assigned SRL172 and 107 (19.3 per 100 person-years) of 386 assigned placebo died. In the Cox's regression analysis, stratified by centre, the hazard ratio of deaths (SRL172/placebo) was 1.03 (95% CI 0.79-1.35). There was no evidence of benefit to the group assigned SRL172.
  
  
  CONCLUSIONS
  Immunotherapy with single-dose SRL172 as an adjunct to standard antituberculosis treatment in HIV-positive adults with pulmonary tuberculosis had no significant effect on survival or bacteriological outcome, though the treatment was safe and well tolerated.
authors.affiliation: University of Zambia-University College London Tuberculosis/HIV Research and Training Project, Lusaka, Zambia.
authors.forename: Alwyn
authors.initials: A
authors.lastname: Mwinga
authors.forename: Andrew
authors.initials: A
authors.lastname: Nunn
authors.forename: Bagrey
authors.initials: B
authors.lastname: Ngwira
authors.forename: Chifumbe
authors.initials: C
authors.lastname: Chintu
authors.forename: David
authors.initials: D
authors.lastname: Warndorff
authors.forename: Paul
authors.initials: P
authors.lastname: Fine
authors.forename: Janet
authors.initials: J
authors.lastname: Darbyshire
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007271:Injections, Intradermal; D008295:Malawi / Q000453:epidemiology; D008297:Male; D010919:Placebos; D016016:Proportional Hazards Models; D013183:Sputum / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D015024:Zambia / Q000453:epidemiology
chemical_list: D000276:Adjuvants, Immunologic; D000995:Antitubercular Agents; D001428:Bacterial Vaccines; D010919:Placebos; C451081:SRL172