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

Charlotte V. Hobbs, Jillian Neal, Solomon Conteh, Liam Donnelly, Jingyang Chen, Kennan Marsh, Lynn Lambert, Sachy Orr-Gonzalez, Jessica Hinderer, Sara Healy, William Borkowsky, Scott R. Penzak, Sumana Chakravarty, Stephen L. Hoffman, Patrick E. Duffy

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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 TMPSMX+ 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.

Original languageEnglish
Article numbere100138
JournalPLoS ONE
Volume9
Issue number7
DOIs
StatePublished - 2 Jul 2014

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    Hobbs, C. V., Neal, J., Conteh, S., Donnelly, L., Chen, J., Marsh, K., Lambert, L., Orr-Gonzalez, S., Hinderer, J., Healy, S., Borkowsky, W., Penzak, S. R., Chakravarty, S., Hoffman, S. L., & Duffy, P. E. (2014). HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. PLoS ONE, 9(7), [e100138]. https://doi.org/10.1371/journal.pone.0100138