The elite controller phenotype.

PURPOSE OF REVIEW: Achieving a functional cure for HIV remains a major challenge. In this context, elite controllers (ECs) - rare people living with HIV who maintain durable virological suppression without antiretroviral therapy - represent a unique and highly informative model. Recent years have seen major advances in the characterization of EC phenotypes across diverse geographic settings, as well as renewed interest in their relevance for HIV cure strategies. This review is considering emerging data refining EC heterogeneity, and the unresolved question of antiretroviral treatment indications in this population.

RECENT FINDINGS: Recent studies highlight the marked heterogeneity among ECs, ranging from persistent controllers with long-term undetectable viral loads to transient or viremic controllers at risk of losing control. Key advances concern the quantitative and qualitative features of the HIV reservoir and the role of both adaptive and innate immune responses. Longitudinal cohorts have also clarified the dynamics of loss of control, and the generally low but nonnegligible burden of non-AIDS-defining comorbidities.

SUMMARY: Elite controllers provide critical insights into mechanisms of durable HIV remission and inform cure-oriented research. Improved stratification of EC phenotypes may help identify individuals approaching spontaneous functional cure. Antiretroviral therapy should be individualized, balancing virological stability, immune activation, comorbidities, and patient preference, while ongoing research aims to translate lessons from ECs into scalable HIV cure strategies.