title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Gilead Sciences, Inc, Foster City, CA, USA. damian.mccoll@gilead.com
authors.forename: Damian J
authors.initials: DJ
authors.lastname: McColl
authors.forename: Nicolas
authors.initials: N
authors.lastname: Margot
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Chen
authors.forename: Jeanette
authors.initials: J
authors.lastname: Harris
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D019259:Lamivudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000068679:Emtricitabine; C098320:efavirenz