A phase IIIb, randomized, open-label study of the antiviral activity and safety of Dolutegravir compared to Lopinavir/Ritonavir both administered with dual nucleoside reverse transcriptase inhibitor therapy in HIV-1 infected adult subjects with treatment failure on first line therapy

Project no.: HIV-NAT 218/GSK-200304 (NCT02227238)

This study is conducted to demonstrate non-inferior antiviral activity at 48 weeks of a dolutegravir (DTG) containing regimen compared to a WHO-recommended standard of care regimen for second line treatment, LPV/RTV + two NRTIs, in HIV-1 infected patients failing first line therapy.

Results: 624 adults were randomized and treated. Subjects were well matched for demographic and baseline characteristics. The IDMC decision had limited impact on the primary endpoint as all LPV/r subjects who switched or discontinued due to the IDMC decision had a viral load value at Week 48/52. At Week 48, 84% (261/312) of subjects on DTG versus 70% (219/312) on LPV/r achieved HIV-1 RNA < 50 c/mL (adjusted difference 13.8%, 95% CI: 7.3% to 20.3%, p < 0.001 for superiority). The difference was primarily driven by lower rates of Snapshot virologic nonresponse (VL ≥ 50 c/mL) in subjects on DTG. 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. Of 11 DTG subjects who met protocol-defined virologic withdrawal criteria through Week 52, one had treatment-emergent primary integrase-strand transfer inhibitor (INSTI) and NRTI resistance mutations while another had INSTI mutations only; in comparison, 30 LPV/r subjects met virologic withdrawal criteria, and 3 had emergent NRTI but no protease inhibitor mutations. (Source: Aboud M, et al., Superior efficacy of dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) compared with lopinavir/ritonavir (LPV/r) plus 2 NRTIs in second-line treatment – 48-week data from the DAWNING Study. Abstract # THPEB040. Presented at AIDS Conference 2018)