Durable efficacy of dolutegravir/rilpivirine switch in subjects with HIV RNA <50 copies/ml and history of K103N mutation

OBJECTIVE: Primary 48-week analyses of the WISARD trial showed maintenance of virological suppression in most participants with K103N mutation when switched from standard regimens to dolutegravir plus rilpivirine (DTG/RPV). In this proof-of-concept pilot study we evaluate 96-week efficacy and safety of DTG/RPV. DESIGN: Open-label, parallel, two-arm, randomized trial across 32 sites in seven European countries. METHODS: Treatment-experienced HIV-1 participants with HIV RNA <50 copies/ml and documented prior K103N mutation, switched to DTG/RPV either immediately (DTG/RPV-I) or deferred after week 48 (DTG/RPV-D [control]; randomized 2 : 1). Endpoints were confirmed virological failure (CVF), virological suppression, safety, and changes in patient-reported outcomes from baseline to weeks 48/96. RESULTS: Of 140 randomized participants (95 DTG/RPV-I, 45 control), 4 had CVF by week 48 (3 DTG/RPV-I, 1 control) and 4 further patients had CVFs by week 96 (2 in each arm). Of the total 8 CVFs through week 96, HIV-1 RNA was ≥400 copies/ml in 4; only one sample amplified with no emergent DTG- or RPV-associated resistance mutations. The other three samples did not amplify due to insufficient sample. The week 96 proportion of subjects with virological suppression was 84.2% for DTG/RPV-I and 73.3% for DTG/RPV-D groups (difference +10.9%, 95% confidence interval -4 to +25.8; P = 0.168). Serious adverse events were infrequent in both groups, and none were considered related to study medication. HRQoL, participant satisfaction, and sleep quality were stable over time and similar in both groups. CONCLUSIONS: Week 96 data confirm that switching to DTG/RPV maintains virological suppression and is safe in most participants with a history of K103N.