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Persistent elite controllers maintain HIV remission due to a unique biological profile, unlike transient controllers who eventually lose control. Understanding this profile is key to identifying potential spontaneous cures in people with HIV (PWHIV).

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Area of Science:

  • Immunology
  • Virology
  • Genomics

Background:

  • Elite controllers represent a unique subset of people with HIV (PWHIV) who naturally control viral load without antiretroviral treatment (ART).
  • Heterogeneity exists within elite controllers, differentiating those with persistent remission from those with transient control.

Purpose of the Study:

  • To delineate the distinct characteristics of persistent elite controllers versus transient elite controllers.
  • To identify biomarkers and mechanisms associated with sustained natural virological control in HIV.

Main Methods:

  • Comparative analysis of metabolomic, proteomic, microRNA (miRNA), immunological, and virological profiles.
  • Assessment of HIV-specific T-cell responses and proviral DNA integration sites.

Main Results:

  • Transient elite controllers show distinct multi-omic profiles and reduced T-cell responses compared to persistent controllers.
  • Persistent elite controllers exhibit a favorable HIV-1 reservoir, with absent or low clonal intact proviruses in transcriptionally repressed genomic regions.
  • Transient elite controllers have a higher proportion of intact proviruses integrated into genic regions.

Conclusions:

  • Characterizing persistent elite controllers is crucial for identifying PWHIV with potential for spontaneous HIV remission.
  • Distinct biological profiles differentiate individuals capable of long-term natural HIV control.