title: Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.
abstract: BACKGROUND
  Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen.
  
  
  METHODS
  We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance.
  
  
  RESULTS
  A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group.
  
  
  CONCLUSIONS
  Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. (Funded by ViiV Healthcare; SINGLE ClinicalTrials.gov number, NCT01263015 .).
authors.affiliation: From the University Health Network, Toronto (S.L.W.); Hospital Clinico Universitario, Santiago de Compostela (A.A.), and Hospital General de Elche and Universidad Miguel Hernández, Alicante (F.G.) - both in Spain; Centre Hospitalier Universitaire Saint-Pierre, Brussels (N.C.); Dr. Victor Babes Infectious and Tropical Diseases Hospital, Bucharest, Romania (D.D.); Medizinisches Versorgungszentrum Karlsplatz HIV Research and Clinical Care Center, Munich, Germany (A.E.); Centre Hospitalier Régional d'Orléans, Orléans, France (L.H.); Antiviral Therapy Unit, Ospedali Riuniti, Bergamo, Italy (F.M.); University of Nebraska Medical Center, Omaha (U.S.); GlaxoSmithKline, Stockley Park, United Kingdom (C.G.); and GlaxoSmithKline, Research Triangle Park, NC (K.P., B.W., S.M., G.N.).
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walmsley
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Dan
authors.initials: D
authors.lastname: Duiculescu
authors.forename: Andrea
authors.initials: A
authors.lastname: Eberhard
authors.forename: Felix
authors.initials: F
authors.lastname: Gutiérrez
authors.forename: Laurent
authors.initials: L
authors.lastname: Hocqueloux
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
authors.forename: Uriel
authors.initials: U
authors.lastname: Sandkovsky
authors.forename: Catherine
authors.initials: C
authors.lastname: Granier
authors.forename: Keith
authors.initials: K
authors.lastname: Pappa
authors.forename: Brian
authors.initials: B
authors.lastname: Wynne
authors.forename: Sherene
authors.initials: S
authors.lastname: Min
authors.forename: Garrett
authors.initials: G
authors.lastname: Nichols
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral / Q000097:blood; D055815:Young Adult; D000099227:Abacavir; D000099226:Dolutegravir
chemical_list: D044966:Anti-Retroviral Agents; D015224:Dideoxynucleosides; D006575:Heterocyclic Compounds, 3-Ring; D019259:Lamivudine; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral; D000099227:Abacavir; D000099226:Dolutegravir