title: A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults.
abstract: BACKGROUND
  HIV-infected, treatment-experienced adults with a history of prior resistance and regimen failure can be virologically suppressed but may require multitablet regimens associated with lower adherence and potential resistance development.
  
  
  METHODS
  We enrolled HIV-infected, virologically suppressed adults with 2-class to 3-class drug resistance and at least 2 prior regimen failures into this phase 3, open-label, randomized study. The primary endpoint was the percentage of participants with HIV-1 RNA <50 copies per milliliter at week 24 [Food and Drug Administration (FDA) snapshot algorithm].
  
  
  RESULTS
  For 135 participants [elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV), n = 89; baseline regimen, n = 46], most of whom were taking a median of 5 tablets/d, simplification to E/C/F/TAF plus DRV was noninferior to continuation of baseline regimens at week 24 (plasma HIV-1 RNA <50 copies per milliliter: 96.6% vs. 91.3%, difference 5.3%, 95.001% CI: -3.4% to 17.4%). E/C/F/TAF plus DRV met prespecified criteria for noninferiority and superiority at week 48 for the same outcome. E/C/F/TAF plus DRV was well tolerated and had an improved renal safety profile compared with baseline regimens, with statistically significant differences between groups in quantitative total proteinuria and markers of proximal tubular proteinuria. Compared with baseline regimens, participants who switched to E/C/F/TAF plus DRV reported higher mean treatment satisfaction scale total scores and fewer days with missed doses.
  
  
  CONCLUSIONS
  This study demonstrated that regimen simplification from a 5-tablet regimen to the 2-tablet, once-daily combination of E/C/F/TAF plus DRV has durable maintenance of virologic suppression and improvements in specific markers of renal safety. Such a strategy may lead to greater adherence and improved quality of life.
authors.affiliation: *The Ruth M. Rothstein CORE Center, Chicago, IL; †Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; ‡Southwest CARE Center, Santa Fe, NM; §Division of Infectious Diseases, Weill Cornell Medicine, New York, NY; and ‖Gilead Sciences, Inc., Foster City, CA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Huhn
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Joel
authors.initials: J
authors.lastname: Gallant
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilkin
authors.forename: Andrew
authors.initials: A
authors.lastname: Cheng
authors.forename: Mingjin
authors.initials: M
authors.lastname: Yan
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhong
authors.forename: Christian
authors.initials: C
authors.lastname: Callebaut
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Custodio
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Fordyce
authors.forename: Moupali
authors.initials: M
authors.lastname: Das
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents