A protease inhibitor (PI)-based antiretroviral regimen has been found to reduce the risk of malaria co-infection among young children in Uganda.
Investigator Jane Achan, of Makerere University College of Health Sciences in Kampala, Uganda, announced the findings during a late-breaker session Monday at the American Society of Tropical Medicine and Hygiene’s 60th Annual Meeting in Philadelphia.
“Despite existing control interventions, HIV-infected individuals living in malaria endemic areas continue to suffer high rates of malaria,” Achan said, adding that antiretroviral therapy (ART) is now increasingly available throughout Africa. “HIV and malaria parasites both encode aspartic class proteases, raising the possibility that HIV protease inhibitors may have antimalarial activity,” she said.
She and her investigative team decided to compare the incidence of malaria among HIV-infected children randomized to receive either:
- a PI-based ART regimen (liponavir plus ritonavir) and two nucleoside reverse transcriptase inhibitors (NRTIs); or
- a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimen (nevirapine or efavirenz) plus two NRTIs.
The open-label study involved 176 HIV-infected children between the ages of two months and five years in Tororo, Uganda – an area of high malaria transmission. Children in both arms received cotrimoxazole and insecticide-treated bed nets. All medical care was provided at a study clinic that was open every day.
The children were followed from September 2009 through July 2011, and investigators found that those who received the PI-based ART experienced a 41 percent reduction in incidence of malaria compared to the group in the NNRTI-based ART group. What is more, even after a malaria episode, the PI-group was 59 percent less likely to experience the hazard of recurrent malaria following treatment with artemether/lumefantrine (AL), a relatively effective and well-tolerated malaria treatment.
Achan said she and her investigative team had a few plausible explanations for the findings:
- The direct antimalarial effect of the liponavir/ritonavir protease inhibitor regimen
- The pharmacokinetic effect of the protease inhibitor regimen on lumefantrine leading to a prolonged post-treatment prophylactic effect following treatment with AL
- An anti-parasitic synergy between the PI regimen and lumefantrine
There were no significant differences in the risk of adverse events following antimalarial therapy between the two ART arms, Achan said.