Open Access Research

Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children

Shereen Katrak12, Anne Gasasira23, Emmanuel Arinaitwe3, Abel Kakuru3, Humphrey Wanzira3, Victor Bigira3, Taylor G Sandison4, Jaco Homsy56, Jordan W Tappero6, Moses R Kamya7 and Grant Dorsey8*

Author Affiliations

1 Oregon Health and Science University, Portland, USA

2 Department of Epidemiology, University of California, Berkeley, USA

3 Makerere University - University of California San Francisco Research Collaboration, Kampala, Uganda

4 Department of Medicine, University of Washington, Seattle, USA

5 Institute for Global Health, University of California, San Francisco, USA

6 Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, USA

7 Department of Medicine, Makerere University Medical School, Kampala, Uganda

8 Department of Medicine, University of California, San Francisco, Box 0811, San Francisco, CA 94143, USA

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Malaria Journal 2009, 8:272  doi:10.1186/1475-2875-8-272

Published: 30 November 2009

Abstract

Background

Artemisinin combination therapy has become the standard of care for uncomplicated malaria in most of Africa. However, there is limited data on the safety and tolerability of these drugs, especially in young children and patients co-infected with HIV.

Methods

A longitudinal, randomized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4-22 months in Tororo, Uganda. Participants were randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes. Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment. This study was registered in ClinicalTrials.gov (registration # NCT00527800).

Results

A total of 122 children were randomized to AL and 124 to DP, resulting in 412 and 425 treatments, respectively. Most adverse events were rare, with only cough, diarrhoea, vomiting, and anaemia occurring in more than 1% of treatments. There were no differences in the risk of these events between treatment groups. Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms. Retreatment for malaria within 17-28 days was associated with an increased risk of vomiting in the DP treatment arm (HR = 6.47, 95% CI 2.31-18.1, p < 0.001). There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis.

Conclusion

Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children.

Trial Registration

ClinicalTrials.gov: NCT00527800; http://clinicaltrials.gov/ct2/show/NCT00527800 webcite