A Comparison of the Phenotypic Susceptibility Profiles of Emtricitabine and Lamivudine

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Emtricitabine (FTC) and lamivudine (3TC) are cytosine nucleoside analogues approved for use in HIV-1 infection. Both compounds select for the M184V/I mutation resulting in high-level resistance. This study compared the phenotypic resistance profiles of FTC and 3TC. Both compounds were tested against clinical samples submitted for routine resistance testing (PhenoSense HIV assay). We evaluated 306 viruses with nucleoside reverse transcriptase inhibitor mutations (NRTI-R) and 100 viruses without resistance mutations (WT). Seventy-two percent had > or = 1 thymidine analogue mutation (TAM), 21% had mixtures at M184, 14% had L74V and 7.5% had K65R. Results were expressed as fold change (FC) in 50% effective concentration compared with the NL4-3 reference. Concordance of FC was evaluated based on biological (99th percentile of the distribution of WT virus population) and clinical cutoffs (FC above which an optimal virological response declines). Against the WT viruses, FTC and 3TC had identical mean FC values relative to the NL4-3 reference of 0.9-fold +/- 0.2 and identical biological cutoffs of 1.4-fold against WT viruses. For NRTI-R isolates, there was a strong linear correlation between FTC and 3TC FC values (r2 = 0.94). Moreover, there was > 90% concordance in resistance calls based on either the biological (1.4-fold) or proposed clinical (3.5-fold) cutoffs among all NRTI-R isolates or isolates with M184V/I mixtures. In the absence of M184V/I, the majority of samples with resistance (> 3.5 FC) exhibited TAMs with a trend toward increased levels of cross-resistance with increasing numbers of TAMs. FTC and 3TC demonstrate nearly identical phenotypic resistance profiles and have the same biological cutoff in this panel of NRTI-R and WT clinical HIV-1 isolates.