The HIV Paradox: Acquired Immunodeficiency, Latent Reservoirs, and Mechanisms of Viral Persistence Why Antiretroviral Therapies Fail to Achieve a Curative Outcome

Despite the transformative success of combination antiretroviral therapy(cART) in controlling HIV replication, infection remains incurable due to the persistence of latent, replication-competent viral reservoirs. This review articulates the central paradox of HIV management—effective suppression without eradication—by deconstructing the biological and immunological architecture of viral persistence. We examine the establishment of latent proviruses within long-lived CD4+ memory T cells and anatomically privileged sanctuary sites, mechanisms that render these reservoirs invisible to both antiretroviral drugs and immune surveillance. The analysis details the pharmacological and immunological limitations of current therapies, distinguishing between the concepts of sterilizing cure and functional remission. By synthesizing foundational and contemporary research, this work provides a critical framework for understanding the barriers to an HIV cure and establishes the conceptual prerequisites for the rational design of next-generation curative strategies, including latency reversal, immune engineering, and reservoir mapping.