HIV-1 protease mutation 82M contributes to phenotypic resistance to protease inhibitors in subtype G

The Journal of Antimicrobial Chemotherapy
Ana Carolina PalmaKristel Van Laethem

Abstract

The purpose of this study was the qualitative and quantitative assessment of the in vitro effect of HIV-1 protease (PR) mutation 82M on replication capacity and susceptibility to the eight clinically available PR inhibitors (PIs). The 82M substitution was introduced by site-directed mutagenesis in wild-type subtype B and G strains, as well as reverted back to wild-type in a therapy-failing strain. The recombinant viruses were evaluated for their replication capacity and susceptibility to PIs. The single 82M mutation within a wild-type subtype B or G background did not result in drug resistance. However, the in vitro effect of single PR mutations on PI susceptibility is not always distinguishable from wild-type virus, and particular background mutations and polymorphisms are required to detect significant differences in the drug susceptibility profile. Consequently, reverting the 82M mutation back to wild-type (82I) in a subtype G isolate from a patient that failed therapy with multiple other PR mutations did result in significant increases in susceptibility towards indinavir and lopinavir and minor increases in susceptibility towards amprenavir and atazanavir. The presence of the 82M mutation also slightly decreased viral repli...Continue Reading

References

Apr 1, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Anna Maria GerettiUNKNOWN UK Collaborative Group on HIV Drug Resistance
Jul 7, 2009·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Ana Carolina PalmaRicardo Jorge Camacho
Jul 28, 2010·Antimicrobial Agents and Chemotherapy·Soo-Yon RheeRobert W Shafer

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Citations

Jul 2, 2009·Journal of the International AIDS Society·Jorge L Martinez-CajasMark A Wainberg
Sep 3, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Dana S ClutterRobert W Shafer
Oct 25, 2013·Expert Review of Anti-infective Therapy·Sarah Megens, Kristel Van Laethem

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