Literature DB >> 27821443

Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1.

Ebere Sonoiki1, Christian Nsanzabana1, Jennifer Legac1, Kirthana M V Sindhe1, Joseph DeRisi2, Philip J Rosenthal3.   

Abstract

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 and a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes.
Copyright © 2016 American Society for Microbiology.

Entities:  

Keywords:  HIV; Plasmodium falciparum; antiretroviral; aspartic protease; drug resistance; drug resistance mechanisms; drug sensitivity; lopinavir; malaria; pfmdr1

Mesh：

Substances：

Year:  2016        PMID： 27821443      PMCID： PMC5192118          DOI： 10.1128/AAC.01949-16

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


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