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.