NEW YORK (Reuters Health) Jan 22 - Protease inhibitors, already valued in treating HIV infection and under investigation as anti-protozoals and anti-cancer agents, now demonstrate new potential as anti-malaria drugs.
A laboratory study by U.S. researchers has shown for the first time that HIV protease inhibitors inhibited the development of preerythrocytic-stage plasmodium parasites. Lopinavir and saquinavir separately had this effect in vitro, and the combination of lopinavir and ritonavir had this effect in mice. The study was published in the January 1 issue of The Journal of Infectious Diseases.
These data are important, "as there is currently no clinically available drug that has an effect on the liver stages in the way that we have demonstrated HIV protease inhibitors have an effect," Dr. Charlotte V. Hobbs of New York University School of Medicine told Reuters Health. "HIV proteases inhibitors are unique in their demonstrated ability to inhibit parasite development in the liver stages, at which point the parasite is initially present in much lower numbers."
Since 2004, published research has shown that HIV protease inhibitors can be effective against plasmodium in the erythrocytic stages of the protozoan's life cycle.
The current researchers found that saquinavir and lopinavir inhibited the development of Plasmodium berghei exo-erythrocytic forms in vitro, but that atazanavir, amprenavir and nelfinavir did not.
In the in vivo part of the study, which used P. yoelii, lopinavir/ritonavir exerted a dose-dependent effect in reducing the burden of liver-stage parasites in mice, while saquinavir alone had no effect, even at high doses.
Dr. Hobbs told Reuters Health that although theories have been proposed, no one knows the exact mechanism by which HIV protease inhibitors affect malaria parasites. "If one could elucidate this mechanism," she said, "one could perhaps develop a further class of antimalarial drugs based on the chemical structure of an HIV protease inhibitor.
J Infect Dis 2009;199:134-141.