title: Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of antiretroviral simplification from a ritonavir-boosted protease inhibitor-based regimen [protease inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); ≥6 months of exposure prior to study entry with no prior treatment failure] to the single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants.
  
  
  METHODS
  Phase 3b, randomized, open-label, international, 48-week switch study.
  
  
  METHODS
  Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12% margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot analysis.
  
  
  RESULTS
  A total of 476 participants were randomized and received at least one dose of study drug. Demographics and baseline characteristics were similar between arms. The primary objective of noninferiority at week 24 was met: HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95% confidence interval -1.6 to 9.1%). Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participant's pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group.
  
  
  CONCLUSIONS
  Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.
authors.affiliation: aNorthwestern University, Feinberg School of Medicine, Chicago, Illinois, USA bBrighton and Sussex University Hospitals, Brighton, UK cUniversity of Pennsylvania, Division of Infectious Diseases, Clinical Trials Unit, Philadelphia, Pennsylvania, USA dChelsea and Westminster Hospital Foundation Trust, London, UK ePeter Ruane, MD, Inc., Los Angeles, California, USA fUniversity Medical Center Hamburg-Eppendorf, Hamburg, Germany gLa Playa Medical Group and Clinical Research, San Diego hKaiser Permanente, Sacramento iGilead Sciences Inc., Foster City, California, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.forename: Jan
authors.initials: J
authors.lastname: Van Lunzen
authors.forename: David
authors.initials: D
authors.lastname: Shamblaw
authors.forename: Jason
authors.initials: J
authors.lastname: Flamm
authors.forename: Ramin
authors.initials: R
authors.lastname: Ebrahimi
authors.forename: Danielle
authors.initials: D
authors.lastname: Porter
authors.forename: Kirsten
authors.initials: K
authors.lastname: White
authors.forename: Jason
authors.initials: J
authors.lastname: Hindman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Elbert
authors.forename: Shampa
authors.initials: S
authors.lastname: De-Oertel
authors.forename: Todd
authors.initials: T
authors.lastname: Fralich
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral