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Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Understanding HIV dynamics is critical for developing a cure.
  • Technical challenges and limited access to fresh tissues have hindered research.
  • HIV reservoirs persist throughout the body, complicating eradication efforts.

Purpose of the Study:

  • To characterize HIV reservoirs and dynamics in various tissues.
  • To reconstruct the spread of HIV within the human body.
  • To identify viral factors associated with HIV dispersal.

Main Methods:

  • Observational study of 6 individuals with HIV (4 on ART, 2 with rebound viremia).
  • Serial blood sampling before rapid autopsy and tissue analysis.
  • Digital droplet PCR, single-genome amplification, and full-length envelope HIV sequencing.
  • Phylogeographic methods and generalized linear models.

Main Results:

  • HIV DNA levels varied across participants and tissues.
  • 605 intact full-length env sequences recovered from blood and 28 tissues.
  • Identical HIV RNA populations emerged in blood after ART cessation, repopulating tissues.
  • Blood and lymphoid tissues were primary sources of HIV dissemination.
  • Viral exchanges occurred within and across the blood-brain barrier.

Conclusions:

  • HIV reservoirs persist in deep tissues, with blood as the main dispersal source.
  • This explains therapy-free remission in some cases after T-cell targeted treatments.
  • Deeper tissue reservoirs remain a challenge for complete HIV eradication.