Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study

Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which t...

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Detalles Bibliográficos
Autores principales: Castagna, Antonella, Maggiolo, Franco, Penco, Giovanni, Wright, David, Mills, Anthony, Grossberg, Robert, Molina, Jean-Michel, Chas, Julie, Durant, Jacques, Moreno, Santiago, Doroana, Manuela, Ait-Khaled, Mounir, Huang, Jenny, Min, Sherene, Song, Ivy, Vavro, Cindy, Nichols, Garrett, Yeo, Jane M., Aberg, J., Akil, B., Arribas, J. R., Baril, J.-G., Blanco Arévalo, J. L., Blanco Quintana, F., Blick, G., Boix Martínez, V., Bouchaud, O., Branco, T., Bredeek, U. F., Castro Iglesias, M., Clumeck, N., Conway, B., DeJesus, E., Delassus, J.-L., De Truchis, P., Di Perri, G., Di Pietro, M., Duggan, J., Duvivier, C., Elion, R., Eron, J., Fish, D., Gathe, J., Haubrich, R., Henderson, H., Hicks, C., Hocqueloux, L., Hodder, S., Hsiao, C.-B., Katlama, C., Kozal, M., Kumar, P., Lalla-Reddy, S., Lazzarin, A., Leoncini, F., Llibre, J. M., Mansinho, K., Morlat, P., Mounzer, K., Murphy, M., Newman, C., Nguyen, T., Nseir, B., Philibert, P., Pialoux, G., Poizot-Martin, I., Ramgopal, M., Richmond, G., Salmon Ceron, D., Sax, P., Scarsella, A., Sension, M., Shalit, P., Sighinolfi, L., Sloan, L., Small, C., Stein, D., Tashima, K., Tebas, P., Torti, C., Tribble, M., Troisvallets, D., Tsoukas, C., Viciana Fernández, P., Ward, D., Wheeler, D., Wilkin, T., Yeni, G.-P., Louise Martin-Carpenter, J., Uhlenbrauck, Gina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Major Articles and Brief Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091579/
https://www.ncbi.nlm.nih.gov/pubmed/24446523
http://dx.doi.org/10.1093/infdis/jiu051
Descripción
Sumario:Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was −1.43 log(10) c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).

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