DAWNING STUDY
DAWNING is a Phase 3b, open-label, parallel-group, non-inferiority, active controlled, multicentre trial for patients with HIV-1 where previous treatment with an NNRTI and two NRTIs has resulted in virological failure (N=624).
This study was designed to assess the safety and efficacy of DTG + 2 NRTIs vs LPV/r + 2 NRTIs (a World Health Organisation recommended regimen) in patients failing first-line therapy with an NNRTI + 2 NRTIs. Primary analysis occurred at Week 48, with secondary analysis taking place at Weeks 24 and 48. After an ad-hoc review of trial data prior to Week 24 interim analysis, the IDMC recommended discontinuation of the LPV/r group because of differences in rates of virologic non-response and increasing differences in rates of protocol-defined virologic failure favouring the DTG group.
The study protocol was amended to allow ongoing LPV/r-treated patients to switch to DTG. The trial was extended to Week 52 and, following on from this, patients could continue on DTG treatment in the open-label continuation phase.1
*Stratification: by HIV-1 RNA (≤ or >100,000 copies/mL), number of fully active NRTIs in the investigator-selected study background regimen (2 or <2).
Primary endpoint:1
Proportion of participants achieving plasma HIV-1 RNA <50 copies/mL at Week 48, using the FDA snapshot algorithm on the ITT-E population (-12% non-inferiority margin).
Results/outcomes:1,2
- DTG + 2 NRTIs is superior to LPV/r + 2 NRTIs in the ITT-E population
- 82% vs 69% achieved virological suppression at Week 24 (P<0.0001)
- 84% vs 70% achieved virological suppression at Week 48 (P<0.0001)
- (adjusted difference 13·8%; 95% CI: 7·3–20·3). Non-inferiority was achieved on the basis of the 95% CI of the adjusted treatment difference having a lower bound greater than −12% (prespecified non-inferiority margin). Because the lower bound of the 95% CI is greater than zero (7·3%), superiority of dolutegravir was also concluded (p<0·0001)
- Median time to viral suppression was significantly shorter in the DTG group vs LPV/r group (29 days vs 111 days, respectively; P<0.0001)
- DTG + 2 NRTIs was generally better tolerated vs LPV/r + 2 NRTIs, with fewer discontinuations
- 4% vs 14% with AEs of Grades 2–4
- 3% vs 6% with AEs leading to discontinuation
- Both groups had 6% of participants reporting serious AEs
References:
- Aboud M, et al. The Lancet. 2019;19:253–264.
- Aboud M et al. IAS 2017; Paris, France. Slides TUAB0105LB
PM-GB-DLL-WCNT-210002 | April 2021
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