Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection
Sharon L Walmsley, Antonio Antela, Nathan Clumeck, Dan Duiculescu, Andrea Eberhard, Felix Gutiérrez, Laurent Hocqueloux, Franco Maggiolo, Uriel Sandkovsky, Catherine Granier, Keith Pappa, Brian Wynne, Sherene Min, Garrett Nichols, SINGLE Investigators, D Baker, R Moore, T Read, N Roth, N Clumeck, E Florence, M Moutschen, L Vandekerckhove, M Boissonnault, B Conway, J De Wet, J Gill, K Kasper, O Rosengren, G Smith, C Tsoukas, S Walmsley, J Gerstoft, F Ajana, J Durant, L Hocqueloux, M-A Khuong-Josses, M Partisani, G Pialoux, Y Yazdanpanah, K Arasteh, A Baumgarten, A Eberhard, S Esser, H Jaeger, B Kuhlmann, B-E Ole Jensen, T Lutz, H-J Stellbrink, C Stephan, A Trein, A Antinori, P Bassi, A Di Biagio, A Lazzarin, F Maggiolo, F Mazzotta, M E van der Ende, D Duiculescu, S Rugina, A Streinu-Cercel, A Antela, J R Arribas, C Barros, J Berenguer, A Cano Sánchez, B Clotet Sala, E Deig Comerma, P Domingo, V Estrada, J Flores Cid, M J Galindo, J L Gomez Sirvent, M A Goenaga, F Gutierrez Rodero, M G Hernández-Mora, S Ibarra Ugarte, M Marquez, S Moreno Guillen, A Ocampo Hermida, J Lopez Aldeguer, J A Oteo Revuelta, J Pasquau, J Portilla, D Podzamczer Palter, M Peñaranda Vera, E Ribera, R Rubio, J Sanz, J Sanz Moreno, V Soriano, M Telenti, R Torres Perea, P Viciana Fernández, J Fox, P Hay, M Johnson, S Kegg, N Nwokolo, S Taylor, A Teague, U Bredeek, J Cade, E DeJesus, H Edelstein, R Elion, J Eron Jr, C Evans, J Feinberg, F Felizarta, C Goulston, B Hanna, W K Henry, C Hicks, G Huhn, R Hsu, T Jefferson, M Johnson, P Johnson, J Kilby, P Kumar, J Lalezari, M Markowitz, C Martorell, C McDonald, J Meier, A Mills, K Mounzer, M Murphy, C Newman, T Nguyen, P O'Keefe, O Osiyemi, C Polk, M Ramgopal, R Redfield, F Rhame, G Richmond, J Rodriguez, U Sandkovsky, S Santiago, A Scarsella, A Scribner, D Shamblaw, G Simon, J Slim, L Sloan, C Small, D Stein, K Tashima, M Tribble, J De Vente, G Voskuhl, M Wohlfeiler, B Young, Sharon L Walmsley, Antonio Antela, Nathan Clumeck, Dan Duiculescu, Andrea Eberhard, Felix Gutiérrez, Laurent Hocqueloux, Franco Maggiolo, Uriel Sandkovsky, Catherine Granier, Keith Pappa, Brian Wynne, Sherene Min, Garrett Nichols, SINGLE Investigators, D Baker, R Moore, T Read, N Roth, N Clumeck, E Florence, M Moutschen, L Vandekerckhove, M Boissonnault, B Conway, J De Wet, J Gill, K Kasper, O Rosengren, G Smith, C Tsoukas, S Walmsley, J Gerstoft, F Ajana, J Durant, L Hocqueloux, M-A Khuong-Josses, M Partisani, G Pialoux, Y Yazdanpanah, K Arasteh, A Baumgarten, A Eberhard, S Esser, H Jaeger, B Kuhlmann, B-E Ole Jensen, T Lutz, H-J Stellbrink, C Stephan, A Trein, A Antinori, P Bassi, A Di Biagio, A Lazzarin, F Maggiolo, F Mazzotta, M E van der Ende, D Duiculescu, S Rugina, A Streinu-Cercel, A Antela, J R Arribas, C Barros, J Berenguer, A Cano Sánchez, B Clotet Sala, E Deig Comerma, P Domingo, V Estrada, J Flores Cid, M J Galindo, J L Gomez Sirvent, M A Goenaga, F Gutierrez Rodero, M G Hernández-Mora, S Ibarra Ugarte, M Marquez, S Moreno Guillen, A Ocampo Hermida, J Lopez Aldeguer, J A Oteo Revuelta, J Pasquau, J Portilla, D Podzamczer Palter, M Peñaranda Vera, E Ribera, R Rubio, J Sanz, J Sanz Moreno, V Soriano, M Telenti, R Torres Perea, P Viciana Fernández, J Fox, P Hay, M Johnson, S Kegg, N Nwokolo, S Taylor, A Teague, U Bredeek, J Cade, E DeJesus, H Edelstein, R Elion, J Eron Jr, C Evans, J Feinberg, F Felizarta, C Goulston, B Hanna, W K Henry, C Hicks, G Huhn, R Hsu, T Jefferson, M Johnson, P Johnson, J Kilby, P Kumar, J Lalezari, M Markowitz, C Martorell, C McDonald, J Meier, A Mills, K Mounzer, M Murphy, C Newman, T Nguyen, P O'Keefe, O Osiyemi, C Polk, M Ramgopal, R Redfield, F Rhame, G Richmond, J Rodriguez, U Sandkovsky, S Santiago, A Scarsella, A Scribner, D Shamblaw, G Simon, J Slim, L Sloan, C Small, D Stein, K Tashima, M Tribble, J De Vente, G Voskuhl, M Wohlfeiler, B Young
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 .).
Source: PubMed