Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study

Antonella Castagna, Franco Maggiolo, Giovanni Penco, David Wright, Anthony Mills, Robert Grossberg, Jean-Michel Molina, Julie Chas, Jacques Durant, Santiago Moreno, Manuela Doroana, Mounir Ait-Khaled, Jenny Huang, Sherene Min, Ivy Song, Cindy Vavro, Garrett Nichols, Jane M Yeo, VIKING-3 Study Group, J Aberg, B Akil, J R Arribas, J-G Baril, J L Blanco Arévalo, F Blanco Quintana, G Blick, V Boix Martínez, O Bouchaud, T Branco, U F Bredeek, M Castro Iglesias, N Clumeck, B Conway, E DeJesus, J-L Delassus, P De Truchis, G Di Perri, M Di Pietro, J Duggan, C Duvivier, R Elion, J Eron, D Fish, J Gathe, R Haubrich, H Henderson, C Hicks, L Hocqueloux, S Hodder, C-B Hsiao, C Katlama, M Kozal, P Kumar, S Lalla-Reddy, A Lazzarin, F Leoncini, J M Llibre, K Mansinho, P Morlat, K Mounzer, M Murphy, C Newman, T Nguyen, B Nseir, P Philibert, G Pialoux, I Poizot-Martin, M Ramgopal, G Richmond, D Salmon Ceron, P Sax, A Scarsella, M Sension, P Shalit, L Sighinolfi, L Sloan, C Small, D Stein, K Tashima, P Tebas, C Torti, M Tribble, D Troisvallets, C Tsoukas, P Viciana Fernández, D Ward, D Wheeler, T Wilkin, G-P Yeni, J Louise Martin-Carpenter, Gina Uhlenbrauck, Antonella Castagna, Franco Maggiolo, Giovanni Penco, David Wright, Anthony Mills, Robert Grossberg, Jean-Michel Molina, Julie Chas, Jacques Durant, Santiago Moreno, Manuela Doroana, Mounir Ait-Khaled, Jenny Huang, Sherene Min, Ivy Song, Cindy Vavro, Garrett Nichols, Jane M Yeo, VIKING-3 Study Group, J Aberg, B Akil, J R Arribas, J-G Baril, J L Blanco Arévalo, F Blanco Quintana, G Blick, V Boix Martínez, O Bouchaud, T Branco, U F Bredeek, M Castro Iglesias, N Clumeck, B Conway, E DeJesus, J-L Delassus, P De Truchis, G Di Perri, M Di Pietro, J Duggan, C Duvivier, R Elion, J Eron, D Fish, J Gathe, R Haubrich, H Henderson, C Hicks, L Hocqueloux, S Hodder, C-B Hsiao, C Katlama, M Kozal, P Kumar, S Lalla-Reddy, A Lazzarin, F Leoncini, J M Llibre, K Mansinho, P Morlat, K Mounzer, M Murphy, C Newman, T Nguyen, B Nseir, P Philibert, G Pialoux, I Poizot-Martin, M Ramgopal, G Richmond, D Salmon Ceron, P Sax, A Scarsella, M Sension, P Shalit, L Sighinolfi, L Sloan, C Small, D Stein, K Tashima, P Tebas, C Torti, M Tribble, D Troisvallets, C Tsoukas, P Viciana Fernández, D Ward, D Wheeler, T Wilkin, G-P Yeni, J Louise Martin-Carpenter, Gina Uhlenbrauck

Abstract

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 log10 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).

Keywords: DTG; dolutegravir; elvitegravir resistance; integrase inhibitor; raltegravir resistance.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

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Source: PubMed

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