HIV Rebound

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HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs
Marie-Angélique De Scheerder
Bram Vrancken 15
Simon Dellicour 15
Timothy Schlub
Eunok Lee
Wei Shao
Sofie Rutsaert
Chris Verhofstede
Tessa Kerre
Thomas Malfait
Dimitri Hemelsoet
Marc Coppens
Annemieke Dhondt
Danny De Looze
Frank Vermassen
Philippe Lemey 16
Sarah Palmer 16

Linos Vandekerckhove


Highlights
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HIV-1 sequences sampled from different reservoirs were compared to rebound viruses in 11 individuals
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Rebound viruses can originate from various cellular and anatomical compartments
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Cellular proliferation is an important driver of HIV persistence
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Cure strategies should take into account the lack of a prominent HIV rebound origin
Summary
Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial. We collected samples from 11 participants and compared the genetic composition of (pro)viruses collected under treatment from different cellular and anatomical compartments with that of plasma viruses sampled during analytical treatment interruption. We found a remarkably heterogeneous source of viral rebound. In addition, irrespective of the compartment or cell subset, genetically identical viral expansions played a significant role in viral rebound. Our study suggests that although there does not seem to be a primary source for rebound HIV, cellular proliferation is an important driver of HIV persistence and should therefore be considered in future curative strategies.


https://doi.org/10.1016/j.chom.2019.08.003