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DTG VERSUS LPV/R IN SECOND LINE (DAWNING): OUTCOMES BY WHO-RECOMMENDED NRTI BACKBONE
Michael Aboud1, Carlos Brites2, Hongzhou Lu3, Khuanchai Supparatpinyo4, Luis Hercilla5, Jörg Sievers6, Maria Claudia Nascimento7, Judy Hopking8, Mark Underwood7, Dannae Brown6, Martin Gartland7, Kim Smith7
1ViiV Healthcare, Branford, CT, USA,2Federal University of Bahia, Salvador, Brazil,3Fudan University, Shanghai, China,4Chiang Mai University, Chiang Mai, Thailand,5Hospital Nacional Alberto Sabogal Sologuren, Callao, Peru,6ViiV Healthcare, Brentford, UK,7ViiV Healthcare, Research Triangle Park, NC, USA,8GlaxoSmithKline, Uxbridge, UK
DAWNING is a non-inferiority study comparing dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) with a WHO-recommended regimen of lopinavir/ritonavir (LPV/r) + 2 NRTIs in HIV-1 infected adults failing first-line therapy (HIV-1 RNA ≥400 copies [c]/mL) of a non-nucleoside reverse transcriptase inhibitor (NNRTI) + 2 NRTIs (ClinicalTrials.gov: NCT02227238).
Subjects were randomised (1:1, stratified by plasma HIV-1 RNA and number of fully active NRTIs) to 52 weeks of open-label treatment with DTG or LPV/r combined with 2 investigator-selected NRTIs, including at least one fully active NRTI based on Screening resistance testing. The primary endpoint was the proportion of subjects achieving HIV‑1 RNA <50 c/mL at Week 48 (Snapshot algorithm) with an interim analysis at Week 24. Post-hoc efficacy analyses were performed based on whether WHO-recommended second-line NRTIs were chosen per subjects' first-line NRTIs; 59 subjects not taking WHO-recommended first-line NRTIs were excluded.
Of 968 subjects screened, only 78 (8%) were screen failures due to not having one fully active NRTI available; 624 were randomised and treated. At Week 24, DTG+2NRTIs was superior to LPV/r+2NRTIs, with 82% (257/312) and 69% (215/312) of subjects, respectively, achieving HIV-1 RNA <50 c/mL (adjusted difference 13.8%, 95% CI: 7.3% to 20.3%, p<0.001). The difference was mainly driven by lower rates of Snapshot virologic non-response in the DTG group. 56% (347/624) of subjects received WHO-recommended second-line NRTIs, and their response rates within each arm were higher than those for subjects who did not. Regardless of WHO-recommended NRTI use, response rates were higher with DTG versus LPV/r-based regimens (Table). The overall safety profile of DTG+2NRTIs was favourable compared to LPV/r+2NRTIs with more drug-related adverse events reported in the LPV/r group. In this analysis, there were no treatment-emergent primary integrase-strand transfer inhibitor or NRTI resistance mutations in the DTG group through the randomisation phase.
In DAWNING, response rates were highest in subjects receiving DTG + WHO-recommended second-line NRTIs. Further, within each arm, subjects had higher response rates when receiving WHO-recommended versus other second-line NRTIs suggesting resistance testing to guide NRTI selection may not be necessary in this population. DAWNING provides important information to help guide second-line treatment decisions in resource-limited settings.