Narrative Review of Two-Drug Regimens in Modern HIV Care: Driving Innovation, Flexibility, and Quality of Life

The treatment goals in human immunodeficiency virus (HIV) care have expanded beyond virological suppression to encompass long-term tolerability, treatment satisfaction, adherence, quality of life and person-centred care. Within this evolving framework, two-drug regimens (2DRs) with oral and long-acting drugs have emerged as an important therapeutic strategy, demonstrating high virological efficacy in selected clinical settings, while reducing cumulative drug exposure and expanding treatment options. Dolutegravir/lamivudine, dolutegravir/rilpivirine and long-acting cabotegravir/rilpivirine are the regimens studied the most, supported by randomised trials and real-world evidence. Beyond efficacy, 2DRs can improve flexibility of care, support adherence, reduce treatment burden and positively affect patient-reported outcomes. Long-acting injectable strategies may be particularly valuable for individuals who face challenges with daily oral adherence or treatment-related stigma. This narrative review summarizes current evidence on the role of oral and injectable 2DRs in key domains including innovation, flexibility, tolerability, adherence and quality of life, while discussing current limitations and future perspectives.