title: HIV-infected ugandan adults taking antiretroviral therapy with CD4 counts >200 cells/μL who discontinue cotrimoxazole prophylaxis have increased risk of malaria and diarrhea.
abstract: BACKGROUND
  Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/μL. However, this practice has not been evaluated in sub-Saharan Africa.
  
  
  METHODS
  Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/μL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/μL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea.
  
  
  RESULTS
  At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/μL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001).
  
  
  CONCLUSIONS
  HIV-infected adults on ART with CD4 counts >200 cells/μL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. Clinical Trials Registration. NCT00119093.
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Entebbe, Uganda. campbellj@ug.cdc.gov
authors.forename: James D
authors.initials: JD
authors.lastname: Campbell
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.forename: Richard
authors.initials: R
authors.lastname: Degerman
authors.forename: Frank
authors.initials: F
authors.lastname: Kaharuza
authors.forename: Willy
authors.initials: W
authors.lastname: Were
authors.forename: Emmy
authors.initials: E
authors.lastname: Muramuzi
authors.forename: George
authors.initials: G
authors.lastname: Odongo
authors.forename: Milton
authors.initials: M
authors.lastname: Wetaka
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mermin
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Tappero
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D018890:Chemoprevention / Q000379:methods*; D003967:Diarrhea / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015994:Incidence; D008288:Malaria / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D018570:Risk Assessment; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014454:Uganda; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination