Laboratory studies have long established that a class of HIV antiretrovirals known as protease inhibitors can cripple the malaria parasite Plasmodium, and researchers from Uganda and the United States wanted to better understand why.
They tested two antiretroviral 'cocktails' on 170 HIV-positive Ugandan children under the age of five. One of the cocktails contained two protease inhibitors lopinavir and ritonavir.
Over the course of the two-year trial, children who received the cocktail containing the inhibitors had a 41 per cent drop in malaria cases compared with children who did not.
The 41 per cent reduction in clinical malaria episodes is both statistically and clinically significant, Paula Brentlinger, a clinician at the University of Washington, Seattle, told ScienceNOW. The fact that it was achieved in one of the most malaria-vulnerable populations in the world is especially heartening.
To their surprise, the researchers found that the two protease inhibitors had a limited impact on the malaria parasite itself. However they found one of the inhibitors ritonavir boosted the longevity in the body of a widely used anti-malarial drug, lumefantrine.
Children who received anti-retroviral cocktails containing ritonavir had five times as much lumefantrine in their bodies a week after receiving the antimalarial.
We think that these higher lumefantrine exposures were really what was driving the protection against recurrent episodes of malaria, said Jane Achan, a researcher at Makerere University, Uganda, who presented the results of the study earlier this month.
Carlos Kent Campbell, head of the Malaria Control Program at PATH, a US-based nonprofit organisation, said bednets remain the most critical prevention strategy and said most children at risk of malaria are not HIV-positive.
But he added that the unanticipated positive consequences of ritonavir may help reduce parasitemia, a leading malaria-related cause of anaemia in young African children.
S. Patrick Kachur, director of the Centre for Disease Control's malaria programme, also said the finding could benefit investigations into long-acting antimalarials for specific populations.