WELBB03 - Oral Abstract Session
Dolutegravir (DTG) is superior to raltegravir (RAL) in ART-experienced, integrase naive subjects: week 48 results from SAILING (ING111762)
Presented by Pedro Cahn (Argentina).
P. Cahn1, A.L. Pozniak2, H. Mingrone3, C. Brites4, J.F. Andrade-Villanueva5, J. Fourie6, M. Ramgopal7, D. Hagins8, J. Valdez Madruga9, T. Newman10, J. Lombaard11, D. Dorey12, M. Underwood13, S. Griffith13, S. Min13
1Fundacion Huesped, Buenos Aires, Argentina, 2Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom, 3Fundacion IDEAA, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, 4Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil, 5Hospital Civil de Guadalajara “Fray Antonio Alcalde”, CUCS, Universidad de Guadalajara, Guadalajara, Mexico, 6Fourie Medical Centre, Dundee, South Africa, 7Midway Immunology and Research Center, Fort Pierce, United States, 8Chatham CARE Center, Savannah, United States, 9Centro de Referencia e Treinamento DST/AIDS, São Paulo, Brazil, 10Instituto de Infectologia Emilio Ribas, São Paulo, Brazil, 11Josha Research, Bloemfontein, South Africa, 12GlaxoSmithKline, Mississauga, Canada, 13GlaxoSmithKline, Research Triangle Park, United States
Background: DTG is an
investigational integrase inhibitor (INI) administered QD that was assessed versus RAL BID in INI-naive patients with ≥2 class resistance
and ongoing virologic replication.
Methods: SAILING was a double-blind, double-dummy, Phase
III study in HIV-1 infected, treatment-experienced, INI-naive adults randomized
1:1 to receive either DTG 50 mg QD or RAL 400 mg BID plus investigator-selected
background regimen of no more than 2 agents, at least one fully active. Primary
endpoint was the proportion of subjects in the modified ITT (mITT) population
achieving HIV-1 RNA < 50 c/mL at Week 48 (FDA-defined Snapshot algorithm). Subjects
were stratified by number of fully active background agents, use of darunavir
without primary protease inhibitor mutations, and Screening HIV-1 RNA (≤, >50,000 c/mL).
subjects were treated in the mITT population (32% female, 42% African American,
46% CDC Class C); median Baseline HIV-1 RNA and CD4+ cell count were 4.18 log10
c/mL and 200 cells/mm3, respectively. The proportion of
subjects with HIV-1 RNA < 50 c/mL in the group receiving DTG (71%) was
statistically superior to the RAL group (64%) [DTG-RAL treatment difference
7.4%, 95% CI: 0.7% to 14.2%, p=0.030]; this was supported
by sensitivity analyses. More protocol defined virologic failures occurred
in the RAL arm (12%) versus the DTG arm (6%); with significantly fewer subjects
failing with emergent INI-resistance on DTG than on RAL (pre-specified and
alpha-controlled: 1% vs 5%, p=0.003). Mean change from Baseline in CD4+ cell
count was +162.4 cells/mm3 (DTG) and +153.2 cells/mm3
(RAL). Most commonly (≥10%) reported adverse events (AEs) were
diarrhea (20% DTG, 18% RAL) and upper respiratory tract infection (11% DTG, 8%
RAL); overall drug related AEs occurred at similar rates (DTG 20%; RAL 23%). Consistent with prior results, there were small
non-progressive mean changes in serum creatinine for DTG. There were similar changes from Baseline in
urine albumin/creatinine ratio in both arms.
Discontinuations due to safety events were 3% (DTG) and 4% (RAL).
Conclusions: Driven by higher virologic
efficacy, DTG was superior to RAL in INI-naive, treatment-experienced subjects
through 48 weeks, with significantly less emergent resistance and similar
safety and tolerability.
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