Effectiveness and safety of two-drug regimens containing an integrase inhibitor and reverse transcriptase inhibitor in a cohort of virologically suppressed people with HIV: Data from the COMBINE-2 study

Objectives: This study assessed real-world effectiveness and safety of switching to dual therapy regimens consisting of an integrase inhibitor (INSTI), and reverse transcriptase inhibitor (RTI), among suppressed people living with HIV in Europe. Methods: This observational cohort enrolled adults with HIV from 28 sites across Europe who were switching to a two-drug regimen of an INSTI plus a nucleoside reverse transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor while suppressed [viral load (VL) <50 copies/mL]. Participants were followed from regimen start date (baseline) until the earliest of 96 weeks, regimen discontinuation, loss to follow-up, or death. The primary endpoints were suppression, low-level viraemia (VL ≥50 to <200 copies/mL), and high-level viraemia (VL ≥200 copies/mL) at 24-, 48- and 96-weeks post-baseline, and virologic failure (VF) within 96 weeks (2 consecutive VLs ≥50 copies/mL or 1 VL ≥50 copies/mL followed by regimen discontinuation). Adverse events and discontinuations were also described. Results: 737 individuals switched to DTG + 3TC (536, 72.7%), DTG + RPV (186, 25.2%) and other INSTI+RTI regimens (15, 2.0%). At 24-,48-, and 96 weeks of follow up, >98% of individuals with VL data maintained suppression; among VLs ≥50 copies/mL, most (19/23; 82.6%) were low-level viraemia. Five individuals (<1%, DTG + 3TC:2; DTG + RPV:3) experienced VF. Forty-seven non-serious drug-related AEs were reported by 38 participants (5.4%); 2 people experienced serious AEs (0.3%). Regimen discontinuations were infrequent (n = 39, 5.3%) and most commonly attributed to tolerability issues (n = 17). Conclusions: Among suppressed people living with HIV in a real-world setting, INSTI+RTI two-drug regimens were highly effective and well tolerated over 96 weeks of follow-up.