7th IAS Conference on HIV Pathogenesis, Treatment and Prevention June 30-July 3, 2013; Kuala Lumpur, Malaysia Dolutegravir (DTG) is Superior to Raltegravir (RAL) in ART- Experienced, Integrase-Naive Subjects: Week 48 Results From SAILING (ING111762) Pedro Cahn, 1 Anton Pozniak, 2 Horacio Mingrone, 3 Carlos Brites, 4 Jaime Federico Andrade-Villanueva, 5 Jan Fourie, 6 Moti Ramgopal, 7 Debbie Hagins, 8 Jose Madruga, 9 Tamara Newman, 10 John Lombaard, 11 David Dorey, 12 Mark Underwood, 13 Sandy Griffith, 13 Sherene Min, 13 on behalf of the extended SAILING study team 1 Fundación Huésped, Buenos Aires, Argentina; 2 Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 3 Fundación IDEAA, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina; 4 Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; 5 Hospital Civil de Guadalajara “Fray Antonio Alcalde,” CUCS, Universidad de Guadalajara, Guadalajara, Mexico; 6 Fourie Medical Centre, Dundee, South Africa; 7 Midway Immunology and Research Center, Fort Pierce, FL, USA; 8 Chatham CARE Center, Savannah, GA, USA; 9 Centro de Referencia e Treinamento DST/AIDS, São Paulo, Brazil; 10 Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; 11 JOSHA Research, Bloemfontein, South Africa; 12-13 GlaxoSmithKline, 12 Mississauga, ON, Canada; 13 Research Triangle Park, NC, USA
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Dolutegravir (DTG) is Superior to Raltegravir (RAL) in ART-Experienced, Integrase-Naive Subjects: Week 48 Results From SAILING (ING111762)
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7th IAS Conference on HIV Pathogenesis, Treatment and PreventionJune 30-July 3, 2013; Kuala Lumpur, Malaysia
Dolutegravir (DTG) is Superior to Raltegravir (RAL) in ART-Experienced, Integrase-Naive Subjects: Week 48 Results From SAILING
(ING111762)Pedro Cahn,1 Anton Pozniak,2 Horacio Mingrone,3 Carlos Brites,4 Jaime Federico
Andrade-Villanueva,5 Jan Fourie,6 Moti Ramgopal,7 Debbie Hagins,8 Jose Madruga,9 Tamara Newman,10 John Lombaard,11 David Dorey,12 Mark Underwood,13 Sandy Griffith,13
Sherene Min,13 on behalf of the extended SAILING study team1Fundación Huésped, Buenos Aires, Argentina; 2Chelsea and Westminster Hospital NHS Foundation Trust, London, UK;
3Fundación 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, FL, USA; 8Chatham CARE Center, Savannah, GA, USA; 9Centro de Referencia e Treinamento DST/AIDS, São Paulo,
Brazil; 10Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; 11JOSHA Research, Bloemfontein, South Africa; 12-13GlaxoSmithKline, 12Mississauga, ON, Canada; 13Research Triangle Park, NC, USA
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
Study Rationale
•Dolutegravir has been shown to be effective in antiretroviral (ART)-naive (SPRING-2 and SINGLE) and integrase inhibitor (INI)-resistant subjects (VIKING-3).
• SAILING was designed to test the efficacy and safety of DTG versus RAL when used with a background regimen of 2 antiretrovirals (1 of which must have been fully active) in ART-experienced, INI-naive subjects with at least 2-class drug resistance.
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
SAILING (ING111762) Study Design
Week 48primary analysis
Randomization Week 24planned interim
a At Screening and a second consecutive test >400 c/mL within 4 months prior to Screening (if Screening HIV-1 RNA >1000 c/mL, no additional HIV-1 RNA assessment was needed). PBO, placebo; BR, background regimen comprising at least 1 and no more than 2 active agents.
HIV ART-experienced, INI-naive
HIV-1 RNA >400 c/mLa
1:1 Randomizationstratified by HIV-1 RNA
(≤ or >50,000), DRV/r use and # of fully
active drugs
DTG 50 mg QD + RAL PBO + BR
RAL 400 mg BID + DTG PBO + BR
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
DTG 50 mg QD(n=354)
RAL 400 mg BID(n=361)
Age, median (y) 42 43Gender, female 30% 34%Race, white 50% 49%
>50,000 c/mL 30% 29%CD4+ count, median (cells/mm3) 205 193
<200 cells/mm3 49% 51%HBV/HCV coinfection 14% 18%Duration prior ART, median (y) 6.7 6.0≥3 Class resistance 47% 51%DRV/r in background regimenDRV/r use without primary PI mutations 72 (20%) 77 (21%)No DRV/r use or DRV/r use with primary PI mutations
282 (80%) 284 (79%)
Baseline Characteristics
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
Subject Accountability Patients screenedN=1441
Not randomizedN=717
Randomized phasePatients randomized
N=724
Patients randomizedto DTG 50 mg QD
N=360
Patients randomizedto RAL 400 mg BID
N=364
Not treatedN=3
Treated (ITT-E)N=357
Patients excluded at site 083523
N=3
Treated (ITT-E)N=362
Not treatedN=2
Patients excluded at site 083523
N=1
Completion status at Week 48299 (84%) completed
55 (16%) withdrew4 adverse event
20 lack of efficacy9 protocol deviation
5 stopping criteria5 lost to follow-up
1 investigator discretion11 withdrew consent
Completion status at Week 48283 (78%) completed
78 (22%) withdrew11 adverse event
42 lack of efficacy6 protocol deviation
3 stopping criteria10 lost to follow-up
1 investigator discretion5 withdrew consent
mITT-EN=354
mITT-EN=361
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
Mean CD4+ change from Baseline was similar between arms: DTG: +162.4 cells/mm3 (n=294); RAL: +153.2 cells/mm3 (n=283).
71%64%
DTG 50 mg QDRAL 400 mg BID
100908070605040302010
0
BL 4 8 12 16 24 32 40 48Week
Prop
ortio
n (%
)
DTG 50 mg QD was statistically superior to RAL 400 mg BID at Week 48.
*Adjusted difference based on stratified analysis adjusting for Baseline HIV-1 RNA (≤50,000 c/mL vs >50,000 c/mL), DRV/r use without primary PI mutations and Baseline PSS (2 vs <2).
Proportion (95% CI) With HIV-1 RNA <50 c/mL (Snapshot, mITT-E)
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
Primary Endpoint: HIV-1 RNA <50 c/mL at Week 48
71
20
9
64
28
9
0
20
40
60
80
Virologic success Virologic non-response
No W48 data*
Perc
enta
ge o
f sub
ject
s (%
)
DTG 50 mg QD (n=354) RAL 400 mg BID (n=361)
95% CI for differenceFavors
RALFavors
DTG
-20% 0 20%
7.40.7 14.2
-12%
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
a Protocol-defined virologic failure or withdrawal because of drug-related adverse events, safety stopping criteria or lack of efficacy.b Protocol-defined virologic failure or withdrawal due to lack of efficacy.
Sensitivity Analyses
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
Renal laboratory valuesChange from Baseline serum creatinine (μmol/L), mean (SD)
11.1 (15.53)b
(n=291)5.1 (12.23)
(n=283)
Change from Baseline urine albumin/creatinine ratio (mg/mmol), mean (SD)
-0.33 (27.51)(n= 260)
-0.56 (31.81)(n=253)
a 16/21 subjects in the DTG arm and 11/14 subjects in the RAL arm were receiving atazanavir or atazanavir/ritonavir.b As previously described, small non-progressive increase in serum creatinine due to OCT2 inhibition
Select Laboratory Abnormalities
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
• DTG once daily has higher virologic efficacy when compared with RAL twice daily in a treatment-experienced, INI-naive population.• 71% on DTG versus 64% on RAL had HIV-1 RNA <50 c/mL at Week 48.
• DTG 50 mg once daily had a similar tolerability and safety profile to RAL twice daily with a wide variety of background regimens in treatment-experienced subjects.• DTG statistical superiority was driven by fewer withdrawals due to
lack of efficacy, lower number of protocol defined virologic failures and lower treatment emergent resistance.
Conclusions
Cahn et al. IAS 2013; Kuala Lumpur, Malaysia. Abstract WELBB03.
• We thank everyone who has contributed to the success of this study, including• All study participants and their families• The SAILING clinical investigators and their staff
• The GSK and ViiV Healthcare study team• This study was funded by ViiV Healthcare
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