title: Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members.
abstract: BACKGROUND
  The effect of cotrimoxazole prophylaxis taken by persons with HIV on community health and antimicrobial resistance is unknown.
  
  
  OBJECTIVE
  To assess the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity, mortality, and antimicrobial resistance of diarrheal pathogens infecting their HIV-negative family members.
  
  
  METHODS
  Prospective cohort in rural Uganda.
  
  
  METHODS
  A total of 879 persons with HIV and 2771 HIV-negative family members received weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole prophylaxis and households were followed for an average of 17 additional months.
  
  
  RESULTS
  During the study, 224 participants with HIV (25%) and 29 household members (1%) died. Mortality among HIV-negative family members < 10 years old was 63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95% confidence interval (CI), 0.14-0.95; P = 0.04]. Malaria among family members was less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI, 0.53-0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45-0.76; P = 0.0001), and hospitalizations (IRR, 0.57; CI, 0.36-0.92; P = 0.02). Death of a parent with HIV was associated with a threefold increase in mortality among HIV-negative children < 10 years old (hazard ratio, 2.9; CI, 1.1-8.1; P = 0.04). Of 134 bacterial isolates from family members before cotrimoxazole treatment, 89 (66%) were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment, 54 (72%) were resistant (P = 0.41).
  
  
  CONCLUSIONS
  Cotrimoxazole prophylaxis taken by persons with HIV was associated with decreased morbidity and mortality among family members. Antimicrobial resistance among diarrheal pathogens infecting family members did not increase. Concerns regarding the spread of bacterial resistance should not impede implementation of cotrimoxazole programs.
authors.affiliation: CDC-Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention (CDC), and Uganda Virus Research Institute, Entebbe, Uganda. jhm7@cdc.gov
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mermin
authors.forename: John
authors.initials: J
authors.lastname: Lule
authors.forename: John Paul
authors.initials: JP
authors.lastname: Ekwaru
authors.forename: Robert
authors.initials: R
authors.lastname: Downing
authors.forename: Peter
authors.initials: P
authors.lastname: Hughes
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bunnell
authors.forename: Samuel
authors.initials: S
authors.lastname: Malamba
authors.forename: Ray
authors.initials: R
authors.lastname: Ransom
authors.forename: Frank
authors.initials: F
authors.lastname: Kaharuza
authors.forename: Alex
authors.initials: A
authors.lastname: Coutinho
authors.forename: Aminah
authors.initials: A
authors.lastname: Kigozi
authors.forename: Robert
authors.initials: R
authors.lastname: Quick
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003967:Diarrhea / Q000401:mortality / Q000517:prevention & control*; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D004351:Drug Resistance; D005190:Family; D005192:Family Health; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014454:Uganda / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination