By: Ed Susman
SEATTLE, WA – Treatment with lopinavir/ritonavir (Kaletra) reduced the risk that HIV-infected children would become co-infected with malaria, researchers said.
Compared with treatment based on non-nucleoside reverse transcriptase inhibitors, therapy with the protease inhibitor-based combination resulted in a 41% decrease in the incidence of malaria, said Jane Achan, MD, lecturer in pediatrics at Makerere University of Health Sciences, Kampala, Uganda.
The incidence rate was 2.25 malaria cases a year among those treated with non-nucleoside reverse transcriptase inhibitors and 1.32 cases a year with those on the protease inhibitor (P=0.04), she reported at the Conference on Retroviruses and Opportunistic Infections.
Achan suggested that lopinavir/ritonavir might have a direct antimalarial effect or it might enhance the antiparasitic effects of lumefatrine, prolonging that drug’s usefulness in the bloodstream. “This study highlights the possible role of ‘pharmaco-enhancement’ as a tool for reducing the burden of malaria in highly endemic settings,” Achan said.
The open-label study was conducted among children in Tororo, Uganda – a region of high malaria incidence. The study population included children ages 2-6 who met standard criteria for the initiation of antiretroviral therapy or who were already treated with antiretrovirals and had suppressed viral loads.
Participants were randomly assigned to either a lopinavir/ritonavir-based regimen or therapies based on either nevirapine (Viramune) or efavirenz (Sustiva). Treatment was provided at a medical clinic daily.
In the trial, 86 children with a median age of 3.1 were assigned to one of the non-nucleoside reverse transcriptase inhibitors, and 84 children with a median age of 2.9 were assigned to lopinavir/ritonavir. Two-thirds of the children were naïve to antiretroviral therapy at baseline.
Achan reported that 176 malaria events were observed among the patients on non-nucleoside reverse transcriptase inhibitors compared with 109 events among the children receiving the protease inhibitors. Differences in risk of infection with malaria began to emerge within 30 days of treatment.
There was a 29% reduction of the first episode of malaria (P=0.14) and a significant reduction in recurrent malaria – 59% (P=0.004).
The overall 41% reduction in malaria was largely based on a significant reduction in recurrent infections within 30 days in those treated with the antimalarial combination of artemether-lumefantrine.
The improvement in malaria control was achieved without an increase in adverse events, Achan said. “There were no significant differences in the risk of adverse events following antimalarial therapy between the two antiretroviral arms except for transient elevations in liver enzymes which were more common in the non-nucleoside reverse transcriptase inhibitor treatment arm and pruritis occurred more often in the protease inhibitor arm,” she said.
“This trial indicates that in areas where malaria is highly prevalent, treatment with lopinavir/ritonavir appears to provide another level of benefit,” Elaine Abrams, MD, professor of pediatrics and epidemiology at Columbia University, New York said.
Although the studies were conducted in areas in which infant HIV prevalence and malaria prevalence is high, Abrams suggested the studies could influence treatment with protease inhibitors in children in Western countries as well.
- MFP Wire Services