title: Infrequent development of drug resistance in HIV-1-infected treatment-naive subjects after 96 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate.
abstract: Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) comprising elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/ml at week 48 that were maintained through week 96. A resistance analysis of the combined Phase III clinical studies through 96 weeks is described here.
  
  
  
  Genotypic and phenotypic susceptibility to antiretrovirals (ARVs) was evaluated for subjects with HIV-1 RNA ≥400 copies/ml at time of virological failure (VF) or early discontinuation.
  
  
  
  Through week 96, VF resistance analyses were conducted for 24 subjects in each arm (2.8%, 24/866 and 2.8%, 24/867; for E/C/F/TAF and E/C/F/TDF arms, respectively). Primary resistance development to ARVs of the regimen occurred in 10 of 24 subjects in the E/C/F/TAF arm, and 8 of 24 subjects in the E/C/F/TDF arm (E/C/F/TAF: M184V/I, n=9; integrase strand-transfer inhibitor resistance-associated mutations [INSTI-RAMs], n=8; K65R/N, n=2; E/C/F/TDF: M184V/I, n=6; INSTI-RAMs, n=5; K65R/N, n=3). The emergent resistance mutations were similar between the treatment arms.
  
  
  
  E/C/F/TAF achieved a high level of virological suppression in HIV-1 treatment-naive subjects through 96 weeks of treatment, with infrequent resistance development and comparable genotypic changes across both the E/C/F/TAF and E/C/F/TDF treatment groups.
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Margot
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cox
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Moupali
authors.initials: M
authors.lastname: Das
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Callebaut
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000069547:Cobicistat; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010755:Organophosphates; D010641:Phenotype; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D010755:Organophosphates; C583447:tenofovir diphosphate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069547:Cobicistat