Kaletra, saquinavir have anti-malarial effects in test tube

Protease inhibitors can give HIV-infected people at least partial protection against malaria, Australian researchers told delegates at last week’s Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.

The 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.

HIV infection and malaria are known to interact in various ways - although researchers do not understand why.

Infection with the malaria parasite causes a rise in viral load in HIV-infected people, while malaria is more frequent and severe among people infected with HIV. Malaria is more likely to kill people with HIV than those who are not HIV-infected.

HIV-infected pregnant women are more likely to develop malaria and have more severe symptoms including fever and anaemia. There is also some evidence that mother-to-child transmission of HIV is affected by malaria but the research is conflicting.

The Australian researchers looked for a possible clinical effect of protease inhibitors against malaria by using the serum from HIV-infected people taking protease inhibitors against the malaria parasite Plasmodium falciparum in vitro. Serum was used at a 40% concentration for standard in vitro culture of a chloroquine-sensitive laboratory strain of P. falciparum, and the anti-malarial chloroquine was used as a comparator.

They found that serum taken from people who were taking antiretroviral therapy which included ritonavir-boosted saquinavir (Invirase) or lopinavir (Kaletra) showed significant antimalarial activity.

Nelfinavir (Viracept), amprenavir (Agenerase) and the NNRTI nevirapine (Viramune) did not inhibit the growth of the malaria parasite.

They hope these drugs might possess enough clinical activity to afford some protection against malaria to HIV-infected people.

But the activity of those PIs which inhibit malaria is described as ‘moderate’ and the researchers point out that the question of whether this effect will be clinically useful has not been answered.

Further studies among people taking these PIs in areas where malaria is endemic are needed.

There are other potential problems, they stress. Whether or not the parasite might develop resistance to PIs is not known.

Also drug interactions are expected to be a problem. In particular ritonavir has ‘significant potential’ to interact with antimalarial medications.

Exactly why some protease inhibitors should be effective against malaria is not fully understood.

But the Plasmodium species all produce protease enzymes which are vital to the parasite’s life cycle, and inhibition of these protease enzymes by HIV protease inhibitors might explain the effect. The researchers added that this may be a potential target for developing an entirely new class of antimalarial drugs.