Year: 2011
Abstract: PS1/2
Category: Treatment Failure and Salvage Therapy

Dolutegravir (DTG, S/GSK1349572) Treatment of Subjects with Raltegravir (RAL) Resistance: Viral Suppression at Week 24 in the VIKING Study
V. Soriano1, J. Cox2, J.J. Eron3, P. Kumar4, C. Katlama5, A. Lazzarin6, I. Poizot-Martin7, G.J. Richmond8, M. Ait-Khaled9, T. Fujiwara10, J. Huang11, S. Min12, C. Vavro12, J.M. Yeo9
1Hospital Carlos III, Madrid, Spain, 2Montreal General Hospital, Montreal, Canada, 3Center for AIDS Research Clinical Care, UNC School of Medicine, Chapel Hill, United States, 4George Town University, Washington, United States, 5Hôpital de La Pitié-Salpêtrière, Paris, France, 6San Raffaele Scientific Institute, Milan, Italy, 7Hôpital Sainte Marguerite, Marseille, France, 8Fort Lauderdale, Fort Lauderdale, United States, 9GlaxoSmithKline, Stockley Park, London, United Kingdom, 10Shionogi & Co., Ltd, Osaka, Japan, 11GlaxoSmithKline, Toronto, Canada, 12GlaxoSmithKline, Research Triangle Park, United States
Objectives: To assess the antiviral activity through Week 24 of DTG given to HIV-infected subjects with RAL resistance.
Methods: Two sequential cohorts of HIV+ adults with genotypic resistance to RAL and to ≥2 other ARV classes at Baseline received DTG 50mg once daily (Cohort I) or twice daily (Cohort II). All continued failing background therapy through to Day 11 which was then to be optimised. The inclusion of at least one fully active drug in the optimised background regimen (OBR) was required for Cohort II. Plasma HIV-1 RNA was measured using the Abbott (LLOD 50 c/mL) and SuperLow (LLOD 2 c/mL) assays.
Results: The baseline characteristics of the 51 subjects enrolled and antiviral responses at Day 11 and Week 24 are provided below.
Self-limited, grade 1 or 2 diarrhoea was the most common AE reported for 3 and 7 subjects in Cohorts I and II, respectively. Four Cohort I and 3 Cohort II subjects experienced SAEs, all considered unrelated to study drug.
Conclusion: DTG exerts potent antiviral activity in highly treatment-experienced, RAL-resistant subjects. An improved Week 24 response rate was observed in Cohort II. DTG was generally well tolerated at both doses. The Cohort II efficacy and safety support the higher potency of DTG 50 mg BID and verify this dose selection for Phase III. A Phase III trial in subjects with RAL and/or elvitegravir resistance is ongoing.

Presenter: Vincente Soriano, Hospital Carlos III, Madrid, Spain