Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and -2 Randomized Clinical Trials.

BACKGROUND The SWORD trials showed that in participants who achieved virologic suppression taking 3- or 4-drug regimens, switching to the 2-drug regimen dolutegravir plus rilpivirine was non-inferior in maintaining HIV-1 RNA <50 copies/mL at the Week 48 primary endpoint. We present pooled Week 148 analysis results from both studies. SETTING SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries. METHODS SWORD-1 and SWORD-2 are identical, open-label, phase III studies. Participants with screening HIV-1 RNA <50 copies/mL for ≥6 months; no prior virologic failure; and no documented resistance-associated major PI, INI, NRTI, or NNRTI mutations or integrase resistance-associated substitution R263K were randomly assigned 1:1 to switch to once-daily dolutegravir 50 mg plus rilpivirine 25 mg on Day 1 (Early-Switch group) or to continue their current antiretroviral regimen and, if virologically suppressed at Week 48, switch to dolutegravir plus rilpivirine at Week 52 (Late-Switch group) until Week 148. RESULTS Using Snapshot algorithm at Week 148, 432/513 (84%) Early-Switch participants (148 weeks of exposure) and 428/477 (90%) Late-Switch participants (96 weeks of exposure) maintained HIV-1 RNA <50 copies/mL. Eleven participants (1%) on dolutegravir plus rilpivirine met the confirmed virologic withdrawal criterion through Week 148 (Early-Switch group, n=8; Late-Switch group, n=3) with no integrase resistance identified. NNRTI resistance-associated mutations were identified in 6 participants (<1%). Drug-related adverse events (grades 2-4) were observed in 31 (6%) Early-Switch and 16 (3%) Late-Switch participants. Significant improvements in bone biomarkers were observed. Significant improvements were observed in renal biomarkers in participants taking tenofovir disoproxil fumarate pre-switch. CONCLUSION Switching to the 2-drug regimen dolutegravir plus rilpivirine maintained virologic suppression for a high proportion of participants through 3 years, with low rates of virologic failure and a well-tolerated safety profile.