Dolutegravir plus Abacavir-Lamivudine for the treatment of HIV-1 infection

Sharon L. Walmsley, Antonio Antela, Nathan Clumeck, Dan Duiculescu, Andrea Eberhard, Felix Gutieŕrez, Laurent Hocqueloux, Franco Maggiolo, Uriel Sandkovsky, Catherine Granier, Keith Pappa, Brian Wynne, Sherene Min, Garrett Nichols

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1807-1818
Number of pages12
JournalNew England Journal of Medicine
Volume369
Issue number19
DOIs
StatePublished - Jan 1 2013

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Lamivudine
Tenofovir
efavirenz
Virus Diseases
HIV-1
RNA
CD4 Lymphocyte Count
Therapeutics
Integrase Inhibitors
Anti-Retroviral Agents
T-Lymphocytes
Safety
Mutation
Sleep Initiation and Maintenance Disorders
Dizziness
Exanthema
Antiviral Agents
dolutegravir
lamivudine drug combination abacavir
Anxiety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Walmsley, S. L., Antela, A., Clumeck, N., Duiculescu, D., Eberhard, A., Gutieŕrez, F., ... Nichols, G. (2013). Dolutegravir plus Abacavir-Lamivudine for the treatment of HIV-1 infection. New England Journal of Medicine, 369(19), 1807-1818. https://doi.org/10.1056/NEJMoa1215541

Dolutegravir plus Abacavir-Lamivudine for the treatment of HIV-1 infection. / Walmsley, Sharon L.; Antela, Antonio; Clumeck, Nathan; Duiculescu, Dan; Eberhard, Andrea; Gutieŕrez, Felix; Hocqueloux, Laurent; Maggiolo, Franco; Sandkovsky, Uriel; Granier, Catherine; Pappa, Keith; Wynne, Brian; Min, Sherene; Nichols, Garrett.

In: New England Journal of Medicine, Vol. 369, No. 19, 01.01.2013, p. 1807-1818.

Research output: Contribution to journalArticle

Walmsley, SL, Antela, A, Clumeck, N, Duiculescu, D, Eberhard, A, Gutieŕrez, 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', New England Journal of Medicine, vol. 369, no. 19, pp. 1807-1818. https://doi.org/10.1056/NEJMoa1215541
Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutieŕrez F et al. Dolutegravir plus Abacavir-Lamivudine for the treatment of HIV-1 infection. New England Journal of Medicine. 2013 Jan 1;369(19):1807-1818. https://doi.org/10.1056/NEJMoa1215541
Walmsley, Sharon L. ; Antela, Antonio ; Clumeck, Nathan ; Duiculescu, Dan ; Eberhard, Andrea ; Gutieŕrez, Felix ; Hocqueloux, Laurent ; Maggiolo, Franco ; Sandkovsky, Uriel ; Granier, Catherine ; Pappa, Keith ; Wynne, Brian ; Min, Sherene ; Nichols, Garrett. / Dolutegravir plus Abacavir-Lamivudine for the treatment of HIV-1 infection. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 19. pp. 1807-1818.
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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 - Gutieŕrez, 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

PY - 2013/1/1

Y1 - 2013/1/1

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.

AB - 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.

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