"When young Tybre Faw discovers Congressman John Lewis and his heroic march across the Edmund Pettus Bridge in the fight for the right to vote -- Tybre is determined to meet him. Tybre's two grandmothers take him on the seven-hour drive to Selma, Alabama, where Lewis invites Tybre to join him in the annual memorial walk across the Bridge. And so begins a most amazing friendship! In rich, poetic language, Andrea Davis Pinkney weaves the true story of a boy with a dream-together with the story of a real-life hero (who himself had a life-altering friendship with Martin Luther King Jr. when he was young!) Keith Henry Brown's deeply affecting paintings bring this inspiring bond between a young activist and an elder Congressman vividly to life. Both John Lewis and Martin Luther King, Jr. have left indelible marks on future generations. Will Tybre be next to carry the mantle?"--
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.
