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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.
AuthorsCharlotte V Hobbs, Tatiana Voza, Alida Coppi, Brian Kirmse, Kennan Marsh, William Borkowsky, Photini Sinnis
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 199 Issue 1 Pg. 134-41 (Jan 01 2009) ISSN: 0022-1899 [Print] United States
PMID19032102 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • HIV Protease Inhibitors
  • Pyrimidinones
  • Lopinavir
  • Ritonavir
Topics
  • Animals
  • Anopheles (parasitology)
  • Female
  • HIV Infections (complications, prevention & control)
  • HIV Protease Inhibitors (therapeutic use)
  • Lopinavir
  • Malaria (complications, prevention & control)
  • Mice
  • Plasmodium (drug effects, growth & development)
  • Plasmodium berghei (drug effects)
  • Plasmodium yoelii (drug effects)
  • Pyrimidinones (therapeutic use)
  • Ritonavir (therapeutic use)

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