Reduced Emergence of the M184V/I Resistance Mutation When Antiretroviral-Naïve Subjects Use Emtricitabine Versus Lamivudine in Regimens Composed of Two NRTIs Plus the NNRTI Efavirenz

Authors:
  • NMNicolas Margot
    Nicolas Margot
  • SCShan-Shan Chen
    Shan-Shan Chen
  • JHJeanette Harris
    Jeanette Harris
  • KBKatyna Borroto-Esoda
    Katyna Borroto-Esoda
  • MMMichael D. Miller
    Michael D. Miller
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Abstract
Purpose: To compare the development of the M184V/I substitution among antiretroviral treatment-naïve patients taking the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine (FTC) or lamivudine (3TC) from three phase 3 clinical trials of dual NRTIs (including either FTC or 3TC) plus the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV). Methods: Study subjects from three phase 3 clinical trials (FTC 301A, GS-99-903, and GS-01-934) were classified as virologic failures (VF) if they had confirmed ≥400 copies/mL of HIV-1 RNA at week 48 or early study drug discontinuation. Subjects with VF were genotyped by population sequencing. The prevalence of the M184V/I substitution in the FTC or 3TC groups was analyzed using Fisher exact test and in multivariate logistic regression analyses. Results: Among the 3 trials, 522 subjects were treated with FTC dosed once daily and 841 subjects were treated with 3TC dosed twice daily. Among VF subjects at week 48, 5/26 (19.2%) FTC-treated subjects and 27/77 (35.5%) 3TC-treated subjects developed the M184V/I mutation (P = .145). Using the denominator of all subjects treated, 5/522 (1.0%) FTC-treated subjects versus 27/841 (3.2%) 3TC-treated subjects developed the M184V/I substitution (P = .009). Multivariate analyses adjusting for baseline viral load, baseline CD4 cell counts, and baseline NRTI resistance showed that treatment with FTC had a significantly lower rate of M184V/I development than treatment with 3TC (odds ratio 0.32; P = .02). Conclusions: The results of this pooled analysis of 3 clinical trials indicate a lower frequency of development of the M184V/I mutation in subjects treated with FTC versus 3TC when combined in regimens containing dual NRTIs and EFV.

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