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Selection in cell culture of darunavir resistant HIV-1 from nine HIV-1 strains harboring Zanaflex (Tizanidine) PI resistance-associated mutations resulted in the overall emergence of 22 mutations in the protease gene, coding for amino acid substitutions L10F, V11I, I13V, I15V, G16E, L23I, V32I, L33F, S37N, M46I, I47V, I50V, F53L, L63P, A71V, G73S, L76V, V82I, I84V, T91AS, and Q92R, of which L10F, V32I, L33F, S37N, M46I, I47V, I50V, L63P, A71V, and I84V were the most prevalent. Other substitutions that developed frequently in Prezistaritonavir virologic failure isolates occurred at Zanaflex (Tizanidine) acid positions V11I, I15V, L33F, I47V, I50V, and L89V. The median darunavir phenotype (fold change from reference) of the Zanaflex (Tizanidine) failure isolates was 4. Amino acid substitutions were also observed in the protease cleavage sites Zanaflex (Tizanidine) the Gag polyprotein of some Prezistaritonavir virologic failure isolates.

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