Longitudinal Outcomes in a Cohort of Ugandan Children Randomized to Artemether-Lumefantrine Versus Dihydroartemisinin-Piperaquine for the Treatment of Malaria

Background. Artemisinin-based combination therapy (ACT) has become the standard of care for the treatment of uncomplicated Plasmodium falciparum malaria. Although several ACT regimens are approved, data guiding optimal choices of ACTs are limited. We compared short- and long-term outcomes in a cohort of young Ugandan children randomized to 2 leading ACTs. Methods. Overall, 312 children were randomized to artemether-lumefantrine or dihydroartemisinin-piperaquine (DP) at the time of the first episode of uncomplicated malaria (median age, 10.5 months). The same treatment was given for all subsequent episodes of uncomplicated malaria and children were followed until they reached 5 years of age. The cohort included a subgroup that was human immunodeficiency virus (HIV) infected (n = 44) or HIV exposed (n = 175) and prescribed trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Outcomes included time to recurrent malaria following individual treatments and the overall incidences of treatments for malaria, complicated malaria, and hospitalizations. Results. Among children not prescribed TMP-SMX prophylaxis, 4443 treatments for malaria were given over 790 person-years following randomization. Treatment with DP was associated with a lower hazard of recurrent malaria over the 84 days after treatment (hazard ratio, 0.66; 95% confidence interval [CI], .61–.70; P < .001). Children randomized to DP had a lower incidence of all treatments for malaria (incidence rate ratio [IRR], 0.85; 95% CI, .75–.96; P = .01), complicated malaria (IRR, 0.12; 95% CI, .04–.39; P < .001), and hospitalizations (IRR, 0.31; 95% CI, .13–.77; P = .01). Among children prescribed TMP-SMX prophylaxis, there were no significant differences in longitudinal outcomes. Conclusions. Compared to artemether-lumefantrine, the use of DP to treat uncomplicated malaria delayed the time to recurrent malaria and reduced the incidences of treatments for malaria, complicated malaria, and hospitalizations. Clinical Trials Registration. NCT00527800.