|Once-daily Dolutegravir versus Darunavir/Ritonavir in Antiretroviral Naive Subjects: 48 Week Subgroup Analyses from FLAMINGO|| |
|B. Clotet1, M.-A. Khuong2, A. Antinori3, J. van Lunzen4, I. Dumitru5, V. Pokrovskiy6, J. Fehr7, R. Ortiz8, M. Saag9, J. Feinberg10, J. Harris11, C. Brennan12, S. Min12, R. Cuffe13|
|1Hospital Universitari Germans Trias i Pujol, Badalona, Spain, 2Hôpital Delafontaine, Saint-Denis, France, 3Istituto Nazionale Malattie Infettive, Roma, Italy, 4Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany, 5Clinical Infectious Diseases Hospital Constanta, Constanta, Romania, 6Central Research Institute for Epidemiology of Rospotrebnadzor, Moscow, Russian Federation, 7Universität Zürich, Zurich, Switzerland, 8Orlando Immunology Center, Orlando, United States, 9University of Alabama, Birmingham, United States, 10University College of Medicine, Cincinnati, United States, 11GlaxoSmithKline, Brentford, United Kingdom, 12GlaxoSmithKlilne, RTP, United States, 13ViiV Healthcare, Brentford, United Kingdom|
|Objective: In HIV-1 infected ART-naive adults, the integrase inhibitor (INI) DTG was superior to EFV in SINGLE and non-inferior to RAL in SPRING-2 with no treatment-emergent INI resistance. FLAMINGO compares DTG with DRV/r. We present the primary endpoint and adverse events leading to withdrawal by stratification factors and key subgroups. |
Methods: A multicenter, randomised, open label, non-inferiority (-12% margin) study of HIV-1 infected ART-naive adults with HIV-1 RNA ≥1000 c/mL and no RT/PI resistance. Patients were randomized 1:1 to DTG 50mg QD or DRV/r 800/100mg QD with investigator-selected TDF/FTC or ABC/3TC. Randomisation was stratified by HIV RNA (≤, >100k c/mL) and NRTI. The primary endpoint was percentage of patients with HIV-1 RNA < 50 c/mL through Week 48 by FDA snapshot.
Results: 484 patients were randomized and treated (242 in each arm); baseline (BL) median age 34 years, 15% female, 28% non-white, 25% RNA >100k c/mL, 33% ABC/3TC.
[Flamingo LB results table]
At Wk 48, 90% of DTG and 83% of DRV/r patients had HIV-1 RNA < 50 c/mL; adjusted difference 7.1 % (95% CI: 0.9, 13.2), demonstrating statistical superiority (p=0.025) according to a pre-specified testing procedure. Subgroup analysis by baseline HIV-1 RNA revealed similar differences in virologic response rates, with a larger treatment difference in favor of DTG in the high viral load group. With the exception of ALT and AST increased in 2 patients receiving DRV/r, no other individual AE leading to withdrawal was reported in more than 1 subject. No treatment emergent genotypic resistance occurred at the time of virologic failure in either arm.
Conclusion: At Wk 48, once-daily DTG was superior to DRV/r in treatment-naive HIV-1 infected adults, with similar effect across stratification factors and key subgroups. A more pronounced treatment difference occurred in individuals with high baseline viral loads. DTG is a new option for first-line HIV treatment.
Bonaventura Clotet , Hospital Universitari Germans Trias i Pujol , Badalona , Spain
Assigned in sessions:
17.10.2013, 14:00-16:00, Parallel Session, PS4, Antiretroviral Therapy I, Bozar (Plenary Hall)