title: Efficacy and safety of three regimens for the prevention of malaria in young HIV-exposed Ugandan children: a randomized controlled trial.
abstract: OBJECTIVE
  Trimethoprim-sulfamethoxazole prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children.
  
  
  METHODS
  An open-label, randomized controlled trial.
  
  
  METHODS
  Tororo, Uganda, a rural area with intense, year-round, malaria transmission.
  
  
  METHODS
  Two hundred infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age).
  
  
  METHODS
  No chemoprevention, monthly sulfadoxine-pyrimethamine, daily trimethoprim-sulfamethoxazole or monthly dihydroartemisinin-piperaquine given from randomization to 24 months of age.
  
  
  METHODS
  The primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrhoeal illness, or respiratory tract infection; prevalence of anaemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped.
  
  
  RESULTS
  During the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% [95% confidence interval (95% CI) 53-80, P < 0.001] for dihydroartemisinin-piperaquine, 49% (95% CI 23-66, P = 0.001) for trimethoprim-sulfamethoxazole and 9% for sulfadoxine-pyrimethamine (95% CI -35 to 38, P = 0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the dihydroartemisinin-piperaquine arm.
  
  
  CONCLUSIONS
  Monthly chemoprevention with dihydroartemisinin-piperaquine was well tolerated and associated with a significant reduction in malaria in young HIV-exposed children.
authors.affiliation: aDepartment of Medicine, Makerere University College of Health Sciences bInfectious Diseases Research Collaboration, Kampala, Uganda cDepartment of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA dDepartment of Pediatrics, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: James
authors.initials: J
authors.lastname: Kapisi
authors.forename: Victor
authors.initials: V
authors.lastname: Bigira
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Clark
authors.forename: Stephen
authors.initials: S
authors.lastname: Kinara
authors.forename: Florence
authors.initials: F
authors.lastname: Mwangwa
authors.forename: Mary K
authors.initials: MK
authors.lastname: Muhindo
authors.forename: Abel
authors.initials: A
authors.lastname: Kakuru
authors.forename: Francesca T
authors.initials: FT
authors.lastname: Aweeka
authors.forename: Liusheng
authors.initials: L
authors.lastname: Huang
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jagannathan
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects; D018890:Chemoprevention / Q000009:adverse effects* / Q000379:methods*; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects; D013413:Sulfadoxine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects; D014454:Uganda; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011739:Pyrimethamine; D011804:Quinolines; D013413:Sulfadoxine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; C001205:fanasil, pyrimethamine drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines