Journal article
Dolutegravir plus Abacavir―Lamivudine for the Treatment of HIV-1 Infection
The New England journal of medicine, Vol.369(19), pp.1807-1818
2013
DOI: 10.1056/NEJMoa1215541
PMID: 24195548
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.
Details
- Title: Subtitle
- Dolutegravir plus Abacavir―Lamivudine for the Treatment of HIV-1 Infection
- Creators
- Sharon L WALMSLEY - University Health Network, Toronto, CanadaAntonio ANTELA - Hospital Clinico Universitario, Santiago de Compostela, SpainKeith PAPPA - GlaxoSmithKline, Research Triangle Park, NC, United StatesBrian WYNNE - GlaxoSmithKline, Research Triangle Park, NC, United StatesSherene MIN - GlaxoSmithKline, Research Triangle Park, NC, United StatesGarrett NICHOLS - GlaxoSmithKline, Research Triangle Park, NC, United StatesNathan CLUMECK - Universitaire Saint-Pierre, Brussels, BelgiumDan DUICULESCU - Dr. Victor Babes Infectious and Tropical Diseases Hospital, Bucharest, RomaniaAndrea EBERHARD - Medizinisches Versorgungszentrum Karlsplatz HIV Research and Clinical Care Center, Munich, GermanyFelix GUTIERREZ - Hospital General de Elche and Universidad Miguel Hernández, Alicante, SpainLaurent HOCQUELOUX - Centre Hospitalier Régional d'Orléans, Orléans, FranceFranco MAGGIOLO - Antiviral Therapy Unit, Ospedali Riuniti, Bergamo, ItalyUriel SANDKOVSKY - University of Nebraska Medical Center, Omaha, United StatesCatherine GRANIER - GlaxoSmithKline, Stockley Park, United KingdomSINGLE Investigators
- Contributors
- J Meier (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.369(19), pp.1807-1818
- Publisher
- Massachusetts Medical Society
- DOI
- 10.1056/NEJMoa1215541
- PMID
- 24195548
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Language
- English
- Date published
- 2013
- Academic Unit
- Infectious Diseases; Epidemiology; Internal Medicine
- Record Identifier
- 9984094506502771
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