PMID- 25393999
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160121
LR  - 20220330
IS  - 1758-2652 (Electronic)
IS  - 1758-2652 (Linking)
VI  - 17
IP  - 4 Suppl 3
DP  - 2014
TI  - Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in 
      treatment-naive HIV-1-positive individuals: 96 week results from FLAMINGO.
PG  - 19490
LID - 10.7448/IAS.17.4.19490 [doi]
LID - 19490 [doi]
AB  - INTRODUCTION: Dolutegravir (DTG) 50 mg once daily was superior to 
      darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through Week 48, with 90% 
      vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025) [1]. We present data 
      through Week 96. MATERIAL AND METHODS: FLAMINGO is a multicentre, randomized, 
      open-label, Phase IIIb non-inferiority study, in which HIV-1-positive ART-naive 
      adults with HIV-1 RNA>/=1000 c/mL and no evidence of viral resistance were 
      randomized 1:1 to receive DTG or DRV/r, with investigator-selected backbone NRTIs 
      (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV-1 RNA (</=100K 
      c/mL) and NRTI backbone. RESULTS: A total of 484 adults were randomized and 
      treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of 
      participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm 
      (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002). Secondary analyses 
      supported primary results: per-protocol [(DTG 83% vs. DRV/r 70%), 95% CI 12.9 
      (5.3, 20.6)] and treatment-related discontinuation = failure [(98% vs. 95%), 95% 
      CI 3.2 (-0.3, 6.7)]. Overall virologic non-response (DTG 8%; DRV/r 12%) and 
      non-response due to other reasons (DTG 12%; DRV/r 21%) occurred less frequently 
      on DTG. As at Week 48, the difference between arms was most pronounced in 
      participants with high baseline viral load (82% vs. 52% response through Week 96) 
      and in the TDF/FTC stratum (79% vs. 64%); consistent responses were seen in the 
      ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none post-Week 48; DRV/r 
      4, two post-Week 48) experienced protocol-defined virologic failure (PDVF; 
      confirmed viral load 200 c/mL on or after Week 24); none had treatment-emergent 
      resistance to study drugs. Most frequent drug-related adverse events (AEs) were 
      diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r 
      (24%) than DTG (10%). Significantly more participants had Grade 2 fasting LDL 
      toxicities on DRV/r (22%) vs. DTG (7%), p<0.001; mean changes in creatinine for 
      DTG (~0.18 mg/dL) observed at Week 2 were stable through Week 96. CONCLUSIONS: 
      Once-daily DTG was superior to once-daily DRV/r in treatment-naive HIV-1-positive 
      individuals, with no evidence of emergent resistance to DTG in virologic failure 
      and relatively similar safety profiles for DTG and DRV/r through 96 Weeks.
FAU - Molina, Jean-Michel
AU  - Molina JM
AD  - Service des Maladies, Infectieuses et Tropicales, Hopital Saint Louis, Paris, 
      France.
FAU - Clotet, Bonaventura
AU  - Clotet B
AD  - HIV Unit, Hospital Universitari Germans Trias i Pujol, Irsicaixa Foundation, UAB, 
      UVIC-UCC, Badalona, Catalonia, Spain.
FAU - van Lunzen, Jan
AU  - van Lunzen J
AD  - Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Lazzarin, Adriano
AU  - Lazzarin A
AD  - Department of Infectious Diseases, IRCCS San Raffaele Via Stamira d'Ancona, 
      Milan, Italy.
FAU - Cavassini, Matthias
AU  - Cavassini M
AD  - Infectious Disease Service, Lausanne University Hospital, Lausanne, Switzerland.
FAU - Henry, Keith
AU  - Henry K
AD  - Department of Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
FAU - Kulagin, Valeriv
AU  - Kulagin V
AD  - Clinical Center for Prevention and Control of AIDS, Krasnodar, Russian 
      Federation.
FAU - Givens, Naomi
AU  - Givens N
AD  - Clinical Statistics, GlaxoSmithKline, Stockley Park, UK.
FAU - Brennan, Clare
AU  - Brennan C
AD  - Infectious Diseases, GlaxoSmithKline, Clinical Development, Research Triangle 
      Park, NC, USA.
FAU - de Oliveira, Carlos Fernando
AU  - de Oliveira CF
AD  - PPD, Pharmacovigilance, Morrisville, NC, USA.
LA  - eng
PT  - Journal Article
DEP - 20141102
PL  - Switzerland
TA  - J Int AIDS Soc
JT  - Journal of the International AIDS Society
JID - 101478566
PMC - PMC4224885
EDAT- 2014/11/14 06:00
MHDA- 2014/11/14 06:01
PMCR- 2014/11/02
CRDT- 2014/11/14 06:00
PHST- 2014/11/14 06:00 [entrez]
PHST- 2014/11/14 06:00 [pubmed]
PHST- 2014/11/14 06:01 [medline]
PHST- 2014/11/02 00:00 [pmc-release]
AID - 19490 [pii]
AID - 10.7448/IAS.17.4.19490 [doi]
PST - epublish
SO  - J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19490. doi: 10.7448/IAS.17.4.19490. 
      eCollection 2014.