Two Drugs Rather Than Three for Maintenance of Virologic Suppression

Current antiretroviral therapy (ART) combinations, usually comprised of three active drugs, are quite effective in achieving suppression of viral replication, but long-term maintenance on the same regimen may lead to drug-related toxicities. To simplify therapy, two-drug combinations have been proposed. The SWORD-1 and SWORD-2 studies were identically designed, open-label, multicenter, industry-sponsored, phase 3, randomized noninferiority trails designed to evaluate the efficacy and safety of dolutegravir plus rilpivirine (DTG-RPV) compared with continuation of the current ART regimen among patients who were virally suppressed (viral load <50 copies/mL). Participants had been on their first or second three-drug ART regimen for at least 6 months but had not previously switched due to virologic failure.

A total of 1339 patients were screened across both studies; 1028 were randomized to switch to DTG-RPV (n = 516) or continue on their current regimen (n = 512), of whom 4 did not receive treatment, resulting in 1024 participants (78% male; 80% white; median age, 43) included in the intention-to-treat analysis. Median time on ART was >4 years, and most regimens included tenofovir and emtricitabine. After 48 weeks, 95% of participants maintained a viral load <50 copies/mL in both treatment groups (94.7% on DTG-RPV vs. 94.9% in the control arm), confirming the noninferiority of DTG-RPV. Adverse events (AEs) were rare in both groups: More participants in the DTG-RPV group had neuropsychiatric AEs (12% vs. 6%) or discontinued therapy due to AEs (3% vs. 1%).