title: Cotrimoxazole prophylaxis and tuberculosis risk among people living with HIV.
abstract: OBJECTIVE
  Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region.
  
  
  METHODS
  We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status.
  
  
  RESULTS
  In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality.
  
  
  CONCLUSIONS
  In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis.
authors.affiliation: Johns Hopkins University School of Medicine and Center for TB Research, Baltimore, Maryland, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.affiliation: Johns Hopkins University School of Medicine and Center for TB Research, Baltimore, Maryland, United States of America.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.affiliation: Johns Hopkins University School of Medicine and Center for TB Research, Baltimore, Maryland, United States of America ; Perinatal HIV Research Unit, Johannesburg, South Africa.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martinson
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination