Diagnostic and Therapeutic Perspectives on Persistent HIV-1 Low-Level Viremia.

While modern antiretroviral therapy achieves high rates of virologic suppression, persistent low-level viremia (pLLV) remains a common clinical scenario that poses distinct diagnostic and therapeutic dilemmas. This review proposes a systematic diagnostic approach to pLLV, beginning with a thorough evaluation of adherence, potential drug-drug interactions, dietary considerations, and resistance profiles. Such a structured assessment is essential to differentiate diverse pathophysiological conditions, particularly in distinguishing active replication-driven failure from reservoir-derived non-suppressible viremia (NSV). Management strategies are tailored to these findings: extrinsic factors, such as suboptimal adherence or pharmacological barriers, are managed through targeted optimization, while intrinsic resistance necessitates switching to fully active regimen. In contrast, NSV is a reservoir-driven process that does not necessitate ART regimen intensification or modification. We also examine key considerations for recently introduced long-acting injectables in the context of pLLV. Furthermore, we address sexual transmission risks, emphasizing that while the risk remains extremely low within the pLLV range, clinical vigilance is crucial given the risks of virologic failure. Successful pLLV management therefore relies on a tailored approach that balances proactive clinical intervention with judicious observation, ensuring virologic control and patient quality of life.