title: HIV protease inhibitors inhibit the development of preerythrocytic-stage plasmodium parasites.
abstract: Recent studies have demonstrated that human immunodeficiency virus (HIV) protease inhibitors (PIs) exert inhibitory effects on erythrocytic stages of the human-malaria parasite Plasmodium falciparum in vitro and on erythrocytic stages of the rodent-malaria parasite Plasmodium chabaudi in vivo. Although it remains unclear how HIV PIs inhibit the parasite, the effect seen on parasite development in the erythrocytic stages is potent. The effect on preerythrocytic stages has not yet been investigated. Using the rodent parasite Plasmodium berghei, we screened a panel of HIV PIs in vitro for effects on the preerythrocytic stages. Our data indicated that the HIV PIs lopinavir and saquinavir affect preerythrocytic-stage parasite development in vitro. We then evaluated the effect of HIV PIs on preerythrocytic stages in vivo using the rodent parasite Plasmodium yoelii. We found that lopinavir/ritonavir had a dose-dependent effect on liver-stage parasite development. Given that sub-Saharan Africa is where the HIV/AIDS pandemic intersects with malaria, these results merit analysis in clinical settings.
authors.affiliation: NYU School of Medicine, Dept. of Pediatrics, Div. of Infectious Disease, 550 First Ave., 8W New Bellevue, NY, NY 10010, USA. hobbsc01@med.nyu.edu
authors.forename: Charlotte V
authors.initials: CV
authors.lastname: Hobbs
authors.forename: Tatiana
authors.initials: T
authors.lastname: Voza
authors.forename: Alida
authors.initials: A
authors.lastname: Coppi
authors.forename: Brian
authors.initials: B
authors.lastname: Kirmse
authors.forename: Kennan
authors.initials: K
authors.lastname: Marsh
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.forename: Photini
authors.initials: P
authors.lastname: Sinnis
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000517:prevention & control*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D061466:Lopinavir; D008288:Malaria / Q000150:complications / Q000517:prevention & control*; D051379:Mice; D010961:Plasmodium / Q000187:drug effects / Q000254:growth & development*; D010962:Plasmodium berghei / Q000187:drug effects; D010967:Plasmodium yoelii / Q000187:drug effects; D011744:Pyrimidinones / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir