Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO)

96 week results from a randomised, open-label, phase 3b study

Jean Michel Molina, Bonaventura Clotet, Jan van Lunzen, Adriano Lazzarin, Matthias Cavassini, Keith Henry, Valeriv Kulagin, Naomi Givens, Carlos Fernando de Oliveira, Clare Brennan

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95% CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]). INTERPRETATION: Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients. FUNDING: ViiV Healthcare and Shionogi & Co.

Original languageEnglish
Pages (from-to)e127-e136
JournalThe Lancet HIV
Volume2
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Ritonavir
HIV Infections
HIV-1
Therapeutics
Tenofovir
Safety
RNA
dolutegravir
Darunavir
Reverse Transcriptase Inhibitors
Drug-Related Side Effects and Adverse Reactions
Viral Load
Nucleosides
Nausea
Headache
Diarrhea
Research Personnel
Delivery of Health Care

ASJC Scopus subject areas

  • Infectious Diseases
  • Epidemiology
  • Immunology
  • Virology

Cite this

Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO) : 96 week results from a randomised, open-label, phase 3b study. / Molina, Jean Michel; Clotet, Bonaventura; van Lunzen, Jan; Lazzarin, Adriano; Cavassini, Matthias; Henry, Keith; Kulagin, Valeriv; Givens, Naomi; de Oliveira, Carlos Fernando; Brennan, Clare.

In: The Lancet HIV, Vol. 2, No. 4, 01.04.2015, p. e127-e136.

Research output: Contribution to journalArticle

Molina, JM, Clotet, B, van Lunzen, J, Lazzarin, A, Cavassini, M, Henry, K, Kulagin, V, Givens, N, de Oliveira, CF & Brennan, C 2015, 'Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study', The Lancet HIV, vol. 2, no. 4, pp. e127-e136. https://doi.org/10.1016/S2352-3018(15)00027-2
Molina, Jean Michel ; Clotet, Bonaventura ; van Lunzen, Jan ; Lazzarin, Adriano ; Cavassini, Matthias ; Henry, Keith ; Kulagin, Valeriv ; Givens, Naomi ; de Oliveira, Carlos Fernando ; Brennan, Clare. / Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO) : 96 week results from a randomised, open-label, phase 3b study. In: The Lancet HIV. 2015 ; Vol. 2, No. 4. pp. e127-e136.
@article{91665845976c477891662b8cba7d5d6d,
title = "Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study",
abstract = "BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12{\%}. If the lower end of the 95{\%} CI was greater than 0{\%}, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80{\%}) of 242 patients in the dolutegravir group and 164 (68{\%}) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95{\%} CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82{\%}] vs 32/61 [52{\%}], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10{\%}] in the dolutegravir group vs 57/242 [24{\%}] in the darunavir plus ritonavir group), nausea (31/242 [13{\%}] vs 34/242 [14{\%}]), and headache (17/242 [7{\%}] vs 12/242 [5{\%}]). INTERPRETATION: Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients. FUNDING: ViiV Healthcare and Shionogi & Co.",
author = "Molina, {Jean Michel} and Bonaventura Clotet and {van Lunzen}, Jan and Adriano Lazzarin and Matthias Cavassini and Keith Henry and Valeriv Kulagin and Naomi Givens and {de Oliveira}, {Carlos Fernando} and Clare Brennan",
year = "2015",
month = "4",
day = "1",
doi = "10.1016/S2352-3018(15)00027-2",
language = "English",
volume = "2",
pages = "e127--e136",
journal = "The Lancet HIV",
issn = "2352-3018",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO)

T2 - 96 week results from a randomised, open-label, phase 3b study

AU - Molina, Jean Michel

AU - Clotet, Bonaventura

AU - van Lunzen, Jan

AU - Lazzarin, Adriano

AU - Cavassini, Matthias

AU - Henry, Keith

AU - Kulagin, Valeriv

AU - Givens, Naomi

AU - de Oliveira, Carlos Fernando

AU - Brennan, Clare

PY - 2015/4/1

Y1 - 2015/4/1

N2 - BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95% CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]). INTERPRETATION: Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients. FUNDING: ViiV Healthcare and Shionogi & Co.

AB - BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95% CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]). INTERPRETATION: Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients. FUNDING: ViiV Healthcare and Shionogi & Co.

UR - http://www.scopus.com/inward/record.url?scp=84937911678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937911678&partnerID=8YFLogxK

U2 - 10.1016/S2352-3018(15)00027-2

DO - 10.1016/S2352-3018(15)00027-2

M3 - Article

VL - 2

SP - e127-e136

JO - The Lancet HIV

JF - The Lancet HIV

SN - 2352-3018

IS - 4

ER -