HIV-1 Protease Inhibitors: Effective Against Malaria?

Article

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 1 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 studys 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 Organizations 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.

Source: IDSA

Recent Videos
Pathogen Playbook Presenter: Sharon Ward-Fore, BS, MS, MT(ASCP), CIC, FAPIC
Mark Wiencek, PhD
Rebecca Crapanzano-Sigafoos, DrPH, CIC, AL-CIP, FAPIC
The CDC’s updated hospital respiratory reporting requirement has added new layers of responsibility for infection preventionists. Karen Jones, MPH, RN, CIC, FAPIC, clinical program manager at Wolters Kluwer, breaks down what it means and how IPs can adapt.
Studying for the CIC using a digital tablet and computer (Adobe Stock 335828989 by NIKCOA)
Infection Control Today's Conversations with the HSPA President, Arlene Bush, CRCST, CER, CIS, SME, DSMD, CRMST
Infection Control Today's Conversations with the HSPA President, Arlene Bush, CRCST, CER, CIS, SME, DSMD, CRMST
Cheron Rojo, BS, FCS, CHL,  CER, CFER, CRCST
Matthias Tschoerner, Dr Sc
Standardizing Cleaning and Disinfection
Related Content