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Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.
N Engl J Med 2013; 369(19):1807-18NEJM

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+Show Affiliations

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.).

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24195548

Citation

Walmsley, Sharon L., et al. "Dolutegravir Plus Abacavir-lamivudine for the Treatment of HIV-1 Infection." The New England Journal of Medicine, vol. 369, no. 19, 2013, pp. 1807-18.
Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807-18.
Walmsley, S. L., Antela, A., Clumeck, N., Duiculescu, D., Eberhard, A., Gutiérrez, F., ... Nichols, G. (2013). Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. The New England Journal of Medicine, 369(19), pp. 1807-18. doi:10.1056/NEJMoa1215541.
Walmsley SL, et al. Dolutegravir Plus Abacavir-lamivudine for the Treatment of HIV-1 Infection. N Engl J Med. 2013 Nov 7;369(19):1807-18. PubMed PMID: 24195548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. AU - Walmsley,Sharon L, AU - Antela,Antonio, AU - Clumeck,Nathan, AU - Duiculescu,Dan, AU - Eberhard,Andrea, AU - Gutiérrez,Felix, AU - Hocqueloux,Laurent, AU - Maggiolo,Franco, AU - Sandkovsky,Uriel, AU - Granier,Catherine, AU - Pappa,Keith, AU - Wynne,Brian, AU - Min,Sherene, AU - Nichols,Garrett, AU - ,, PY - 2013/11/8/entrez PY - 2013/11/8/pubmed PY - 2013/11/13/medline SP - 1807 EP - 18 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 369 IS - 19 N2 - 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 .). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/24195548/Dolutegravir_plus_abacavir-lamivudine_for_the_treatment_of_HIV-1_infection L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1215541?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -