HIV Protease Inhibitors Inhibit the Development of Preerythrocytic‐Stage Plasmodium Parasites
1Saul Krugman Department of Pediatric Infectious Disease and Immunology and 2Department of Medical Parasitology, New York University, and 3Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York; 4Division of Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois
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.
Received 23 January 2008; accepted 25 February 2008; electronically published 25 November 2008.
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Potential conflicts of interest: K.M. is an employee of Abbott Laboratories. All other authors report no potential conflicts.
Presented in part: 56th American Society of Tropical Medicine and Hygiene Conference, 12–16 November 2006 (abstract 2546).
Financial support: National Institutes of Health (NIH; grant R01AI056840 to P.S., NIH Center for AIDS Research Grant P30 AI027742 to P.S. and C.V.H., NIH Institutional Grant T32 07382 to C.V.H. [noncontemporaneously with the previously mentioned grant P30 AI027742], and NIH Training Grant T32 AI07180 to T.V.).
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W.B. and P.S. contributed equally to the writing of this article.