Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study.
BACKGROUND
Dolutegravir has been shown to be non-inferior to an integrase inhibitor and superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI). In FLAMINGO, we compared dolutegravir with darunavir plus ritonavir in individuals naive for antiretroviral therapy.


METHODS
In this multicentre, open-label, phase 3b, non-inferiority study, HIV-1-infected antiretroviral therapy-naive adults with HIV-1 RNA concentration of 1000 copies per mL or more and no resistance at screening were randomly assigned (1:1) to receive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily, with investigator-selected tenofovir-emtricitabine or abacavir-lamivudine. Randomisation was stratified by screening HIV-1 RNA (≤100,000 or >100,000 copies per mL) and nucleoside reverse transcriptase inhibitor (NRTI) selection. The primary endpoint was the proportion of patients with HIV-1 RNA concentration lower than 50 copies per mL (Food and Drug Administration [FDA] snapshot algorithm) at week 48 with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, NCT01449929.


RESULTS
Recruitment began on Oct 31, 2011, and was completed on May 24, 2012, in 64 research centres in nine countries worldwide. Of 595 patients screened, 484 patients were included in the analysis (242 in each group). At week 48, 217 (90%) patients receiving dolutegravir and 200 (83%) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 copies per mL (adjusted difference 7·1%, 95% CI 0·9-13·2), non-inferiority and on pre-specified secondary analysis dolutegravir was superior (p=0·025). Confirmed virological failure occurred in two (<1%) patients in each group; we recorded no treatment-emergent resistance in either group. Discontinuation due to adverse events or stopping criteria was less frequent for dolutegravir (four [2%] patients) than for darunavir plus ritonavir (ten [4%] patients) and contributed to the difference in response rates. The most commonly reported (≥10%) adverse events were diarrhoea (dolutegravir 41 [17%] patients vs darunavir plus ritonavir 70 [29%] patients), nausea (39 [16%] vs 43 [18%]), and headache (37 [15%] vs 24 [10%]). Patients receiving dolutegravir had significantly fewer low-density lipoprotein values of grade 2 or higher (11 [2%] vs 36 [7%]; p=0·0001).


CONCLUSIONS
Once-daily dolutegravir was superior to once-daily darunavir plus ritonavir. Once-daily dolutegravir in combination with fixed-dose NRTIs represents an effective new treatment option for HIV-1-infected, treatment-naive patients.


BACKGROUND
ViiV Healthcare and Shionogi & Co.
IrsiCaixa, Hospital Universitari "Germans Trias i Pujol", Badalona, UAB, Universitat de Vic, Catalonia, Spain. Electronic address: bclotet@irsicaixa.es.
Bonaventura
B
Clotet
University of Cincinnati, Cincinnati, OH, USA.
Judith
J
Feinberg
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Jan
J
van Lunzen
Hôpital Delafontaine, Saint-Denis, France.
Marie-Aude
MA
Khuong-Josses
National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Roma, Italy.
Andrea
A
Antinori
Clinical Infectious Diseases Hospital, Constanta, Romania.
Irina
I
Dumitru
Central Research Institute for Epidemiology, Moscow, Russia.
Vadim
V
Pokrovskiy
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Jan
J
Fehr
Orlando Immunology Center, Orlando, FL, USA.
Roberto
R
Ortiz
Department of Medicine, Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA.
Michael
M
Saag
GlaxoSmithKline, Stockley Park, Uxbridge, Middlesex, UK.
Julia
J
Harris
GlaxoSmithKline, Research Triangle Park, NC, USA.
Clare
C
Brennan
Shionogi & Company, Ltd, Osaka, Japan.
Tamio
T
Fujiwara
GlaxoSmithKline, Research Triangle Park, NC, USA.
Sherene
S
Min
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003404:Creatinine / Q000378:metabolism; D000069454:Darunavir; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D012709:Serum Albumin / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult; D000099226:Dolutegravir
D019380:Anti-HIV Agents; D003404:Creatinine; D000069454:Darunavir; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D019438:Ritonavir; D012709:Serum Albumin; D013449:Sulfonamides; D000099226:Dolutegravir