Efficacy of second-line dolutegravir plus 2 nucleoside reverse transcriptase inhibitors by baseline nucleoside reverse transcriptase inhibitor resistance and nucleoside reverse transcriptase inhibitor use in the DAWNING study

Background In the DAWNING study, dolutegravir + 2 nucleoside reverse transcriptase inhibitors (NRTIs) demonstrated superior efficacy at Week 48 and a favourable safety profile compared with lopinavir/ritonavir + 2 NRTIs in adults with HIV-1 failing first-line therapy of a non-nucleoside reverse transcriptase inhibitor + 2 NRTIs. Methods Participants at 58 centres in 13 countries were randomised (1:1) to 52 weeks of open-label treatment with dolutegravir or lopinavir/ritonavir 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 participants achieving HIV-1 RNA <50 copies/ml at Week 48 (Snapshot algorithm). Post-hoc efficacy analyses were performed based on baseline NRTI resistance profile and second-line NRTI use. Results Of 624 participants randomised and treated, 499 (80%) received <2 active NRTIs at Baseline. NRTI resistance was present in 561 participants (90%). Among participants receiving lamivudine or emtricitabine in the presence of M184V/I, 85% (187/220) of participants on dolutegravir versus 72% (152/210) on lopinavir/ritonavir had HIV-1 RNA <50 copies/ml at Week 48 (difference, 12.6%; 95% CI: 4.9–20.3%). High responses were also observed in the dolutegravir group, when zidovudine or tenofovir disoproxil fumarate were included in the background regimen in the presence of thymidine analogue mutations or K65R, respectively; however, participant numbers in these subgroups were small. Conclusions Response rates were high in participants receiving dolutegravir + 2 NRTIs as second-line treatment regardless of pre-existing resistance to one of the NRTIs, including in participants using lamivudine or emtricitabine in the presence of M184V/I.