Efficacy and safety of three regimens for the prevention of malaria in young HIV-exposed Ugandan children: a randomized controlled trial

AIDS. 2014 Nov 28;28(18):2701-9. doi: 10.1097/QAD.0000000000000497.


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.

Design: An open-label, randomized controlled trial.

Setting: Tororo, Uganda, a rural area with intense, year-round, malaria transmission.

Participants: 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).

Intervention: No chemoprevention, monthly sulfadoxine-pyrimethamine, daily trimethoprim-sulfamethoxazole or monthly dihydroartemisinin-piperaquine given from randomization to 24 months of age.

Main outcome measures: 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.

Conclusion: Monthly chemoprevention with dihydroartemisinin-piperaquine was well tolerated and associated with a significant reduction in malaria in young HIV-exposed children.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects*
  • Artemisinins / administration & dosage
  • Artemisinins / adverse effects
  • Chemoprevention / adverse effects*
  • Chemoprevention / methods*
  • Child, Preschool
  • Cohort Studies
  • Drug Combinations
  • Female
  • Humans
  • Infant
  • Malaria / prevention & control*
  • Male
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / adverse effects
  • Quinolines / administration & dosage
  • Quinolines / adverse effects
  • Sulfadoxine / administration & dosage
  • Sulfadoxine / adverse effects
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • Uganda


  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Quinolines
  • fanasil, pyrimethamine drug combination
  • dihydroartemisinin
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Sulfadoxine
  • piperaquine
  • Pyrimethamine