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.
Bibliographical noteFunding Information:
This work was funded by ViiV Healthcare and Shionogi & Co. We thank the study patients, and their families and caregivers for participation in the study. We also thank Krischan J Hudson for being lead medical writer, and Justin Koteff and Meredith MacPherson for editorial assistance during the development of this report.
J-MM has participated in advisory boards for Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare and has received research grants from Gilead Sciences and Merck. BC has received research grants from Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare and personal fees from Abbot and Janssen. JvL has received honoraria, served as an adviser, and received research funding from AbbVie, Bionor, Boehringer Ingelheim, Bristol-Myers Squibb, Genetic Immunity, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme, Roche, ViiV Healthcare, and Vision7. MC has served as an expert for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck Sharp & Dohme; has received honoraria for such services; and has received unrestricted research grants from Bristol-Myers Squibb, Gilead Sciences, and Merck Sharp & Dohme. KH has received research support from Gilead Sciences and ViiV Healthcare. NG is an employee of GlaxoSmithKline. CFdO is as an employee of PPD and acted in the study as part of PPD's contractual relationship with GlaxoSmithKline. CB is an employee of and holds stock in GlaxoSmithKline. AL and VK declare no competing interests.
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