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HIV-1 protease inhibitors: Effective against malaria?

Protease inhibitors used to treat HIV-1 infection may also be effective for treatment or prevention of malaria, according to a study published in the December 15 issue of The Journal of Infectious Diseases, now available online. The study found protease inhibitors inhibited the growth of P. falciparum, the malaria parasite that causes most disease. These findings may also expose a previously unexplored vulnerability in the parasite that could lead to a new class of anti-malarial drug. While the effects of such drugs on co-infection need to be investigated, the study's findings may be especially significant in sub-Saharan Africa and other areas of the developing world where there are high rates of HIV and malaria co-infection.

Scientists from the Queensland Institute of Medical Research tested the effects of the protease inhibitors saquinavir, ritonavir, nelfinavir, amprenavir, and indinavir, as well as the non-nucleoside reverse transcriptase inhibitor nevirapine, on a drug-resistant line of P. falciparum. Saquinavir, ritonavir, and indinavir all inhibited parasite growth in vitro at levels routinely achieved in human patients, with saquinavir and ritonavir showing the most potent effect on the parasite. Saquinavir was most effective in the study and was equally effective on chloroquine-sensitive and -resistant parasite lines, while nelfinavir and amprenavir did not demonstrate anti-malarial activity. The research builds on a previous study that demonstrated antiretroviral agents can reduce the adhesion of P. falciparum-infected erythrocytes to endothelial surfaces.

The authors believe that the antiretroviral protease inhibitors attack the malaria parasite in ways that current antimalarial treatments do not. While the mode of antimalarial action of the drugs was not uncovered in the study, the authors hypothesize that the antiretrovirals inhibit an aspartyl protease, which helps the parasite digest hemoglobin and is located on the food vacuole of the
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Contact: Steve Baragona
sbaragona@idsociety.org
703-299-0412
Infectious Diseases Society of America
8-Nov-2004


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