title: Effect of cotrimoxazole on mortality in HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in low- and middle-income countries through a systematic review and meta-analysis.
  
  
  METHODS
  PubMed and Embase were searched for randomized controlled trials and prospective and retrospective cohort studies that compared mortality or morbidity in HIV-infected individuals aged ≥ 13 years on cotrimoxazole and ART and on ART alone. The Newcastle-Ottawa Quality Assessment Scale was used to assess selection, confounding and measurement bias. Publication bias was assessed using Egger's and Begg's tests. Sensitivity analysis was performed because the I-squared statistic indicated substantial heterogeneity in study results. A random-effects model was used for meta-analysis.
  
  
  RESULTS
  Nine studies were included. Begg and Egger P-values for the seven that reported the effect of cotrimoxazole on mortality were 0.29 and 0.49, respectively, suggesting no publication bias. The I-squared statistic was 93.2%, indicating high heterogeneity in study results. The sensitivity analysis showed that neither the follow-up duration nor the percentage of individuals with World Health Organization stage 3 or 4 HIV disease at baseline explained the heterogeneity. The summary estimate of the effect of cotrimoxazole on the incidence rate of death was 0.42 (95% confidence interval: 0.29-0.61). Since most studies followed participants for less than 1 year, it was not possible to determine whether cotrimoxazole can be stopped safely after ART-induced immune reconstitution.
  
  
  CONCLUSIONS
  Cotrimoxazole significantly increased survival in HIV-infected adults on ART. Further research is needed to determine the optimum duration of cotrimoxazole treatment in these patients.
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, USA.
authors.forename: Amitabh B
authors.initials: AB
authors.lastname: Suthar
authors.forename: Reuben
authors.initials: R
authors.lastname: Granich
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mermin
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Rie
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016001:Confidence Intervals; D014943:Global Health; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D009026:Mortality / Q000639:trends; D016017:Odds Ratio; D013223:Statistics as Topic; D013997:Time Factors; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D044966:Anti-Retroviral Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination