Suchergebnisse

1. A brief introduction to vortex dynamics and turbulence / H. Keith Moffatt -- 2. Geophysical and environmental fluid dynamics / Tieh-Yong Koh and Paul F. Linden -- 3. Weather and climate / Emily Shuckburgh -- 4. Dynamics of the Indian and Pacific oceans / Swadhin Behera and Toshio Yamagata -- 5. The hurricane-climate connection / Kerry Emanuel -- 6. Transport and mixing of atmospheric pollutants / Peter H. Haynes -- 7. Extreme rain events in mid-latitudes / Gerd Tetzlaff, Janek Zimmer, and Robin Faulwetter -- 8. Dynamics of hydro-meteorological and environmental hazards / A. W. Jayawardena -- 9. Tsunami modeling and forecasting techniques / Pavel Tkalich and Dao My Ha -- 10. Rouge waves / F. Dias, T. J. Bridges, and J. M. Dudley.

IntroductionDolutegravir (DTG) 50 mg once daily was superior to darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through Week 48, with 90% vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025) [1]. We present data through Week 96.Material and MethodsFLAMINGO is a multicentre, randomized, open‐label, Phase IIIb non‐inferiority study, in which HIV‐1‐positive ART‐naïve adults with HIV‐1 RNA≥1000 c/mL and no evidence of viral resistance were randomized 1:1 to receive DTG or DRV/r, with investigator‐selected backbone NRTIs (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV‐1 RNA (≤100K c/mL) and NRTI backbone.ResultsA total of 484 adults were randomized and treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002). Secondary analyses supported primary results: per‐protocol [(DTG 83% vs. DRV/r 70%), 95% CI 12.9 (5.3, 20.6)] and treatment‐related discontinuation = failure [(98% vs. 95%), 95% CI 3.2 (−0.3, 6.7)]. Overall virologic non‐response (DTG 8%; DRV/r 12%) and non‐response due to other reasons (DTG 12%; DRV/r 21%) occurred less frequently on DTG. As at Week 48, the difference between arms was most pronounced in participants with high baseline viral load (82% vs. 52% response through Week 96) and in the TDF/FTC stratum (79% vs. 64%); consistent responses were seen in the ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none post‐Week 48; DRV/r 4, two post‐Week 48) experienced protocol‐defined virologic failure (PDVF; confirmed viral load 200 c/mL on or after Week 24); none had treatment‐emergent resistance to study drugs. Most frequent drug‐related adverse events (AEs) were diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r (24%) than DTG (10%). Significantly more participants had Grade 2 fasting LDL toxicities on DRV/r (22%) vs. DTG (7%), p<0.001; mean changes in creatinine for DTG (~0.18 mg/dL) observed at Week 2 were stable through Week 96.ConclusionsOnce‐daily DTG was superior to once‐daily DRV/r in treatment‐naïve HIV‐1‐positive individuals, with no evidence of emergent resistance to DTG in virologic failure and relatively similar safety profiles for DTG and DRV/r through 96 Weeks.