Dolutegravir (DTG) has shown good efficacy and tolerability among treatment-experienced adults with HIV. Most HIV-infected adults in Kenya with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) failure are on ritonavir-boosted protease inhibitor (PI/r)-based second line regimens. We evaluated the efficacy and safety of switching virally suppressed adults from a second-line PI/r-containing regimen to a DTG-containing regimen, without prior drug resistance testing.
The Second-line Switch to DTG (2SD) study is an open-label, randomized, active-controlled, non-inferiority trial conducted at four sites in Kenya. Eligible participants were HIV-1 infected adults (? 18 years) who were virally suppressed (plasma HIV RNA < 50 copies/mL) for at least 12 weeks prior to enrolment and on a second-line regimen of PI/r + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks, and without prior integrase inhibitor exposure. Participants were randomized (1:1) to switch to DTG or continue their pre-enrollment PI/r; pre-enrollment NRTIs continued in both arms. The primary endpoint was proportion of participants with plasma HIV-1 RNA of ? 50 copies/mL at week 48 in the intention-to-treat-exposed (ITT-E) population using the FDA snapshot algorithm and a non-inferiority margin of 4%.
Between Feb 10 and Sep 3, 2020, 795 participants were randomized and 791 were treated (397 DTG, 394 PI/r) and included in ITT-E analysis. All participants were black and 524 (66%) were female, with baseline characteristics balanced between arms. At week 48, the proportion of participants with HIV-1 RNA ? 50 copies/mL was 5.0% (20/397) in the DTG arm and 5.1% (20/394) in the PI/r arm (treatment difference [95% confidence interval], -0.04% [-3.09 to 3.02]), meeting non-inferiority criteria (Table 1). No participants with protocol-defined virological failure had detectable genotypic resistance to the study drug at time of failure in either arm. Treatment-related adverse events (AE) occurred in 88 (23%) participants on DTG and 76 (20%) participants on PI/r; treatment-related grade 3 or 4 AEs were similar (6.0% on DTG; 7.1% on PI/r), with no treatment-related serious AEs in either arm. Participants discontinuing study drug due to any AE was 1 (0.3%) on DTG and 3 (0.8%) on PI/r.
Switching from PI/r to DTG may be an effective and safe strategy for treatment-experienced virally suppressed adults with no prior INSTI-exposure, even without knowledge of prior resistance.