Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1.
Ebere SonoikiChristian NsanzabanaJennifer LegacKirthana M V SindheJoseph L DerisiPhilip J RosenthalPublished in: Antimicrobial agents and chemotherapy (2016)
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.
Keyphrases
- plasmodium falciparum
- copy number
- hiv infected
- antiretroviral therapy
- hiv positive
- human immunodeficiency virus
- hiv aids
- mitochondrial dna
- genome wide
- hiv infected patients
- men who have sex with men
- hepatitis c virus
- young adults
- dna methylation
- south africa
- hiv testing
- protein protein
- gene expression
- small molecule
- genome wide identification