Background: DAWNING is a non-inferiority study conducted to compare a protease inhibitor-sparing regimen of DTG+2NRTIs with a current WHO-recommended regimen of LPV/RTV+2NRTIs in HIV-1 infected subjects failing first-line therapy of a non-nucleoside reverse transcriptase inhibitor (NNRTI) + 2 NRTIs ( NCT02227238). An Independent Data Monitoring Committee (IDMC) performed periodic reviews of data to protect the ethical and safety interests of subjects.
Methods: Adult subjects failing first-line therapy, with HIV-1 RNA ≥400 copies(c)/mL, were randomised (1:1, stratified by Baseline plasma HIV-1 RNA and number of fully active background NRTIs) to 52 weeks of open-label treatment with DTG or LPV/RTV combined with an investigator-selected dual NRTI background, including at least one fully active NRTI. An IDMC review was performed, which included data from 98% (612/627 randomised) of subjects through 24 weeks on therapy.
Results: At Week 24, 78% of subjects on DTG versus 69% on LPV/RTV achieved HIV-1 RNA < 50 c/mL (adjusted difference 9.6%, 95% CI: 2.7% to 16.4%, p=0.006 for superiority). The difference was primarily driven by lower rates of Snapshot virologic non-response in the DTG group. The safety profile of DTG+2NRTIs was favourable compared to LPV/RTV+2NRTIs with more drug-related adverse events (AEs) reported in the LPV/RTV group, mainly due to higher rates of gastrointestinal disorders.
Following review of Week 24 data and large subsets of data from Weeks 36 and 48, the IDMC recommended discontinuation of the LPV/RTV arm due to persistent differences in rates of Snapshot virologic non-response and protocol-defined virologic failure (PDVF) favouring the DTG arm.

Week 24 outcomesDTG (N=307)LPV/RTV (N=305)
Snapshot virologic success240 (78%)210 (69%)
Snapshot virologic non-response36 (12%)64 (21%)
Data in window not <50 c/mL33 (11%)59 (19%)
Discontinued for other reason while not <50 c/mL or change in ART3(1%)5 (2%)
Snapshot no virologic data31 (10%)31 (10%)
Discontinued due to AE or death5 (2%)14 (5%)
Discontinued for other reason or missing data during window but on study26 (8%)17 (6%)
PDVF5/312 (2%)12/312 (4%)
Drug-related AEs45/314 (14%)107/310 (35%)
[Week 24 outcomes]

Conclusions: The IDMC recommended discontinuation of the LPV/RTV arm due to superior efficacy of DTG+2NRTIs and the potential to harm subjects on LPV/RTV based on available data. Final Week 24 results of this study will be presented. DAWNING provides important information to help guide second-line treatment decisions in resource-limited settings.