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PLoS One. 2014 Jul 2;9(7):e100138. doi: 10.1371/journal.pone.0100138. eCollection 2014.

HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo.

Author information

  • 1Laboratory of Malaria Immunology and Vaccinology, National Institutes of Health/National Institute of Allergy and Infectious Diseases, Rockville, Maryland, United States of America.
  • 2AbbVie Inc., North Chicago, Illinois, United States of America.
  • 3Division of Infectious Disease and Immunology, Department of Pediatrics, New York University School of Medicine, New York, New York, United States of America.
  • 4Clinical Center Pharmacy Department, Clinical Pharmacokinetics Research Laboratory, National Institutes of Health/National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
  • 5Sanaria, Inc. Rockville, Maryland, United States of America.

Abstract

We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts.

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