title: Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.
abstract: OBJECTIVE
  Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF).
  
  
  METHODS
  SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48.
  
  
  RESULTS
  Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed.
  
  
  CONCLUSIONS
  Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance data are unavailable.
authors.affiliation: 1 Gilead Sciences Inc. , Foster City, California.
authors.forename: Danielle P
authors.initials: DP
authors.lastname: Porter
authors.forename: Jonathan
authors.initials: J
authors.lastname: Toma
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tan
authors.forename: Owen
authors.initials: O
authors.lastname: Solberg
authors.forename: Suqin
authors.initials: S
authors.lastname: Cai
authors.forename: Rima
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Kristen
authors.initials: K
authors.lastname: Andreatta
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lie
authors.forename: Susan K
authors.initials: SK
authors.lastname: Chuck
authors.forename: Frank
authors.initials: F
authors.lastname: Palella
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: White
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D000068678:Emtricitabine, Rilpivirine, Tenofovir Drug Combination / Q000627:therapeutic use*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D000068678:Emtricitabine, Rilpivirine, Tenofovir Drug Combination; D012367:RNA, Viral
keywords: SPIRIT; historical genotype; proviral DNA; resistance; rilpivirine; switch