title: Safety of discontinuing cotrimoxazole prophylaxis among HIV infected adults on anti-retroviral therapy in Uganda (COSTOP trial): Design.
abstract: BACKGROUND
  Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design.
  
  
  METHODS
  COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm(3) are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events.
  
  
  CONCLUSIONS
  Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations.
  
  
  CONCLUSIONS
  This paper describes the design and methodological considerations important for the conduct of CTX cessation studies.
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: Zacchaeus.Anywaine@mrcuganda.org.
authors.forename: Zacchaeus
authors.initials: Z
authors.lastname: Anywaine
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: Andrew.Abaasa@mrcuganda.org.
authors.forename: Andrew
authors.initials: A
authors.lastname: Abaasa
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: Jonathan.Levin@mrcuganda.org.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levin
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: Ronnie.Kasirye@mrcuganda.org.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Kasirye
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: Anatoli.Kamali@mrcuganda.org.
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; London School of Hygiene and Tropical Medicine, London, UK. Electronic address: Heiner.Grosskurth@lshtm.ac.uk.
authors.forename: Heiner
authors.initials: H
authors.lastname: Grosskurth
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: Paula.Munderi@mrcuganda.org.
authors.forename: Paula
authors.initials: P
authors.lastname: Munderi
authors.affiliation: MRC Clinical Trials Unit at University College London, UK. Electronic address: a.nunn@ucl.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nunn
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D012107:Research Design; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*; D014454:Uganda
chemical_list: D044966:Anti-Retroviral Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: Antiretroviral treatment; Cotrimoxazole cessation study design; Cotrimoxazole prophylaxis; HIV infection; Stopping cotrimoxazole; Uganda