Simplified and long-acting antiretroviral strategies across the HIV prevention and care continuum: clinical applications and future directions

Lifelong antiretroviral therapy has transformed human immunodeficiency virus (HIV) infection into a chronic manageable condition. However, maintaining durable virological suppression while reducing lifelong treatment burden remains a major challenge. Simplified and long-acting antiretroviral strategies have emerged to reduce treatment burden and expand individualized care, but their increasing complexity calls for a comprehensive evaluation of their clinical roles and implementation challenges. This review summarizes the virological basis of current antiretroviral therapy through an overview of the HIV replication cycle and corresponding antiviral drug targets. Simplified and long-acting antiretroviral strategies across the HIV prevention and care continuum are then reviewed, with emphasis on clinical applications, patient selection, resistance considerations, hepatitis B virus coinfection, and implementation challenges. While these strategies reduce medication burden, they also redistribute treatment burden by increasing the need for virological monitoring, resistance assessment, structured follow-up, and healthcare delivery support. Simplified and long-acting antiretroviral strategies are expanding individualized options across HIV prevention and care. Continued optimization of these approaches will require balancing reduced treatment burden with sustained virological suppression through evidence-based regimen selection, long-term monitoring, and the development of next-generation antiviral strategies.