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Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.
N Engl J Med. 2013 Nov 07; 369(19):1807-18.NEJM

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.).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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., Hocqueloux, L., Maggiolo, F., Sandkovsky, U., Granier, C., Pappa, K., Wynne, B., Min, S., & Nichols, G. (2013). Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. The New England Journal of Medicine, 369(19), 1807-18. https://doi.org/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 -