HIV Treatment Paradigm Shifts over the Past 40 Years.

Objectives: This review summarizes the evolution of human immunodeficiency virus (HIV) treatment over the past 40 years, tracing its transition from a fatal infectious disease to a chronic condition and outlining current therapeutic trends that characterize the paradigm shift in care. Methods: Key milestones in HIV therapy were examined through a narrative review, beginning with the introduction of zidovudine in 1987 and extending to highly active antiretroviral therapy (HAART) and recent long-acting injectable agents. Results: The adoption of triple-drug HAART in 1996 addressed the resistance challenges of monotherapy and substantially reduced HIV-related morbidity and mortality. Since the mid-2010s, integrase strand transfer inhibitor (INSTI)-based single-tablet regimens have delivered potent viral suppression, strong resistance barriers, and improved treatment convenience, yielding success rates exceeding 90%. In addition, the implementation of the "Treat All" strategy and the "U=U (Undetectable=Untransmittable)" principle has enhanced individual health and supported broader epidemic control. Conclusions: Current HIV therapy continues to evolve beyond viral suppression toward patient-centered approaches, including two-drug regimens and long-acting injectables, to address unmet needs and enhance quality of life.