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.

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.

• Authors: Moses R Kamya, James Kapisi, Victor Bigira, Tamara D Clark, Stephen Kinara, Florence Mwangwa, Mary K Muhindo, Abel Kakuru, Francesca T Aweeka, Liusheng Huang, Prasanna Jagannathan, Jane Achan, Diane V Havlir, Philip J Rosenthal, Grant Dorsey
• Journal: AIDS (London, England) (AIDS) Vol. 28 Issue 18 Pg. 2701-9 (Nov 28 2014) ISSN: 1473-5571 [Electronic] England
• PMID: 25493596 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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