Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency
作者： Katherine A. Sutherland , Dami A. Collier , Daniel T. Claiborne , Jessica L. Prince , Martin J. Deymier
DOI: 10.1038/SREP38153
关键词:
摘要: The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility protease inhibitors (PI), a critical class of antiretrovirals that will be used in up 2 million individuals as second-line therapy sub Saharan Africa by 2020. Given subtype C represents around half all infections globally, we examined PI viruses from treatment-naive individuals. was measured single round infection assay full-length, replication competent MJ4/gag chimeric viruses, encoding the 142 nucleotides pro derived 20 patients Zambia-Emory HIV Research Project acute cohort. Ten-fold variation PIs atazanavir lopinavir observed with EC50s ranging 0.71-6.95 nM for atazanvir 0.64-8.54 nM lopinavir. Ten amino acid residues Gag correlated EC50 (p < 0.01), which 380 K 389I showed modest impacts on vitro drug susceptibility. Finally significant relationship between capacity but not darunavir. Our findings demonstrate large PI-naive appears correlate efficiency could impact clinical outcomes.
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