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

作者：Sonoiki Ebere; Nsanzabana Christian; Legac Jennifer; Sindhe Kirthana M V; DeRisi Joseph; Rosenthal Philip J^*

来源：Antimicrobial Agents and Chemotherapy, 2017, 61(1): UNSP e01949-16.

DOI：10.1128/AAC.01949-16

• malaria
• Plasmodium falciparum
• drug sensitivity
• drug resistance
• pfmdr1
• aspartic protease
• antiretroviral
• lopinavir
• HIV
• drug resistance mechanisms

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 similar to 9 months, with similar to 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.

• 出版日期2017-1