Altered Plasmodium falciparum sensitivity to the antiretroviral protease inhibitor lopinavir associated with polymorphisms in pfmdr1 [PublishAheadOfPrint]

The HIV protease inhibitor lopinavir inhibits Plasmodium falciparum aspartic proteases (plasmepsins) and parasite development, and children receiving lopinavir-ritonavir experienced fewer episodes of malaria than those receiving other antiretroviral regimens. Resistance to lopinavir was selected in vitro over ~9 months, with ~4-fold decreased sensitivity. Whole genome sequencing of resistant parasites showed a mutation and increased copy number in pfmdr1, a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes.

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