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GENVOYA(elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)tablets(二十六)
bine: The antiviral activity of emtricitabine against laboratory and clinical isolates of HIV-1 was assessed in T lymphoblastoid cell lines, the MAGI-CCR5 cell line, and primary peripheral blood mononuclear cells. The EC50 values for emtricitabine were in the range of 0.0013–0.64 microM. Emtricitabine displayed antiviral activity in cell culture against HIV-1 clades A, B, C, D, E, F, and G (EC50 values ranged from 0.007–0.075 microM) and showed strain specific activity against HIV-2 (EC50 values ranged from 0.007–1.5 microM).
Tenofovir Alafenamide (TAF): The antiviral activity of TAF against laboratory and clinical isolates of HIV-1 subtype B was assessed in lymphoblastoid cell lines, PBMCs, primary monocyte/macrophage cells and CD4-T lymphocytes. The EC50 values for TAF ranged from 2.0 to 14.7 nM.
TAF displayed antiviral activity in cell culture against all HIV-1 groups (M, N, O), including sub-types A, B, C, D, E, F, and G (EC50 values ranged from 0.10 to 12.0 nM) and strain specific activity against HIV-2 (EC50 values ranged from 0.91 to 2.63 nM).
Resistance
In Cell Culture
Elvitegravir: HIV-1 isolates with reduced susceptibility to elvitegravir have been selected in cell culture. Reduced susceptibility to elvitegravir was associated with the primary integrase substitutions T66A/I, E92G/Q, S147G, and Q148R. Additional integrase substitutions observed in cell culture selection included D10E, S17N, H51Y, F121Y, S153F/Y, E157Q, D232N, R263K, and V281M.
Emtricitabine: HIV-1 isolates with reduced susceptibility to emtricitabine have been selected in cell culture. Reduced susceptibility to emtricitabine was associated with M184V or I substitutions in HIV-1 RT.
Tenofovir Alafenamide (TAF): HIV-1 isolates with reduced susceptibility to TAF have been selected in cell culture. HIV-1 isolates selected by TAF expressed a K65R substitution in HIV-1 RT, sometimes in the presence of S68N or L429I substitutions; in addition, a K70E substitution in HIV-1 RT was observed.
In Clinical Trials
In Treatment-Naïve Subjects:
In a pooled analysis of antiretroviral-naïve subjects receiving GENVOYA in Studies 104 and 111, genotyping was performed on plasma HIV-1 isolates from all subjects with HIV-1 RNA greater than 400 copies per mL at confirmed virologic failure, at Week 96, or at time of early study drug discontinuation. As of Week 96, the development of genotypic resistance to elvitegravir, emtricitabine, or TAF was observed in 10 of 19 subjects with eva luable resistance data from paired baseline and GENVOYA treatment-failure isolates (10 of 866 subjects [1.2%]) compared with 9 of 15 treatment-failure isolates from subjects with eva luable resistance data in the STRIBILD treatment group (9 of 867 subjects [1.0%]). Of the 10 subjects with resistance development in the GENVOYA group, the resistance-associated substitutions that emerged were M184V/I (N=9) and K65R/N (N=2) in reverse transcriptase and T66T/A/I/V (N=2), E92Q (N=4), E138K (N=1), Q148Q/R (N=1) and N155H (N=2) in integrase. Of the 9 subjects with resistance development in the STRIBILD group, the resistance-associated substitutions that emerged were M184V/I (N=6) and K65R/N (N=3) in reverse transcriptase and E92Q (N=2), E138K (N=3), Q148R (N=2), and N155H/S (N=2) in integrase. In both treatment groups, most subjects who developed substitutions associated with resistance to elvitegravir also developed emtricitabine resistance-associated substitu |
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