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.
Details
Serval ID
serval:BIB_56AFF9065EE0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
Lancet. Hiv
Working group(s)
FLAMINGO study team
Contributor(s)
Khuong-Josses MA., Molina JM., Pialoux G., Raffi F., Reynes J., Yeni P., Kern W., Stephan C., Van Lunzen J., Antinori A., D'Arminio Monforte A., Di Perri G., Guaraldi G., Lazzarin A., Melendez-Rivera I., Morales Ramirez J., Santana-Bagur J., Duiculescu D., Preotescu L., Rugina S., Kozyrev O., Kulagin V., Pokrovskiy V., Shuldyakov A., Voronin E., Clotet B., Gatell J., Podzamczer D., Rubio R., Viciana P., Cavassini M., Fehr J., Furrer H., Bellos N., Blick G., Brar I., Dietz C., Dretler R., Elion R., Eron J., Feinberg J., Georgescu G., Scribner A., Hagins D., Henry W., Martorell C., Mayer C., McCurdy L., Mills A., Murphy M., Newman C., Ortiz R., Pierone G., Rana A., Saag M., Shalit P., Simon G., Sloan L., Stephens J., Tebas P., Towner W., Tribble M., Warner D., Wilkin A., Young B.
ISSN
2352-3018 (Electronic)
ISSN-L
2352-3018
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
2
Number
4
Pages
e127-e136
Language
english
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.
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.
Keywords
Adolescent, Adult, Analysis of Variance, Anti-HIV Agents/administration & dosage, Darunavir/administration & dosage, Drug Administration Schedule, Drug Resistance, Viral/drug effects, Drug Therapy, Combination, Female, HIV Infections/drug therapy, HIV Infections/immunology, HIV-1, Heterocyclic Compounds, 3-Ring/administration & dosage, Humans, Male, Ritonavir/administration & dosage, Treatment Outcome, Viral Load/drug effects
Pubmed
Web of science
Create date
24/11/2015 18:22
Last modification date
20/08/2019 15:10
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