HIV-1 protease inhibitors: Effective against malaria?

November 08, 2004

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 parasite. Further investigation may not only provide a better knowledge of how to treat co-infected patients with protease inhibitors, but could also lead to a new type of malaria drug that would target the parasite in novel ways.

The World Health Organization's "3 by 5" program intends to treat three million HIV-infected people, primarily in the developing world, with antiretrovirals by the year 2005. The authors suggest that individuals treated under programs such as this may also gain an anti-parasitic benefit. At the same time, they acknowledge that their study does not address the concern that protease inhibitors may have immunological side effects that could hamper parasite removal.

The authors warn that the clinical application of their novel findings should be made with caution. They are currently carrying out further studies on the interactions of protease inhibitors and current antimalarial agents in order to optimize the drugs' beneficial effects on both HIV and malaria infections.
-end-
Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. It is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Alexandria, Va., IDSA is a professional society representing more than 7,500 physicians and scientists who specialize in infectious diseases. Nested within the IDSA, the HIV Medicine Association (HIVMA) is the professional home for more than 2,600 physicians, scientists and other health care professionals dedicated to the field of HIV/AIDS. HIVMA promotes quality in HIV care and advocates policies that ensure a comprehensive and humane response to the AIDS pandemic informed by science and social justice.

Infectious Diseases Society of America

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.