title: Baseline antiretroviral resistance mutations and treatment-emergent resistance in HIV-1 RNA-suppressed patients switching to EVG/COBI/FTC/TDF or continuing on their PI-, NNRTI-, or RAL-based regimen.
abstract: BACKGROUND
  Stably suppressed HIV-1-infected patients that switched to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) from regimens containing FTC/TDF plus a ritonavir-boosted protease inhibitor (PI + RTV), nonnucleoside reverse transcriptase inhibitor (NNRTI), or raltegravir in phase 3 studies STRATEGY-PI, STRATEGY-NNRTI, and GS-US-236-0123 maintained high rates of virologic suppression through 48 weeks. In this article, resistance analyses for these studies are described.
  
  
  METHODS
  HIV-1 historical genotypes obtained before therapy initiation were analyzed for preexisting/transmitted resistance (-R) in protease and reverse transcriptase (RT) and subtype. Patients with resistance to FTC/TDF were excluded. Viral isolates with HIV-1 RNA ≥400 copies per milliliter at confirmed virologic failure, discontinuation, or week 48 were analyzed for protease, RT, and integrase genotype and phenotype.
  
  
  RESULTS
  Historical genotypes from 626/628 subjects that switched to EVG/COBI/FTC/TDF indicated 25% had ≥1 primary resistance mutation in protease and/or RT. NNRTI-R was identified in 15%, NRTI-R in 8.3%, and PI-R in 3.7% of subjects. Week 48 virologic success rates (HIV-1 RNA <50 copies per milliliter) were 94% for all patients treated with EVG/COBI/FTC/TDF, 94% with preexisting resistance, 93% with subtype B, and 96% with non-B subtypes. Altogether, 2 subjects qualified for postbaseline resistance analyses. Neither had emergent resistance, and both resuppressed to HIV-1 RNA <50 copies per milliliter with no change in therapy.
  
  
  CONCLUSIONS
  Switching antiretroviral regimens to EVG/COBI/FTC/TDF in HIV-1 RNA-suppressed FTC/TDF-sensitive patients resulted in maintained virologic suppression through 48 weeks. Similar virologic success rates were achieved irrespective of the presence of preexisting resistance mutations or subtype. The lack of emergent resistance through 48 weeks supports utility of EVG/COBI/FTC/TDF for treatment-experienced patients seeking regimen modification or simplification.
authors.affiliation: Gilead Sciences Inc., Foster City, CA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Andreatta
authors.forename: Rima
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Michael E
authors.initials: ME
authors.lastname: Abram
authors.forename: Thai
authors.initials: T
authors.lastname: Nguyen
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents