Simplification of antiretroviral therapy: comparative review of two-drug and three-drug regimens in HIV treatment.

Combined antiretroviral therapies have revolutionized HIV management. Triple-drug regimens (3DR) have been the cornerstone of HIV treatment, which provide durable virologic suppression, reduce HIV-related morbidity and mortality, and improve immune reconstitution. However, 3DR are associated to long-term toxicities. In certain settings, two-drug regimens (2DR) present non-inferior virological efficacy compared to 3DR and may improve tolerability and adherence. In this review, we examine the efficacy, safety, and patient-centered outcomes of 3DR and 2DR, and the potential benefits of transitioning from triple to dual therapy regimens in people with HIV. We conducted a literature search on PubMed, EMBASE, and the Cochrane Library databases for studies published between January 2010 and June 2024. Overall data support the non-inferior efficacy of 2DR to 3DR in the management of HIV, with no evidence of an increased risk of subclinical failure with dual therapy. Switching from 3DR to 2DR may reduce the risk of drug interactions and toxicity. Within the 2DR, the long-acting therapies represent the most innovative dual therapy since they simplify the treatment by reducing from triple to dual therapy along shifting from daily pills to bi-monthly injections. Long-acting 2DR are effective, provide high levels of satisfaction, and improve adherence and quality of life.