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No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Norton, Nicholas J 
Bandara, Mikaila 

Abstract

The persistence of infected T cells harbouring intact HIV proviruses is the barrier to the eradication of HIV. This reservoir is stable over long periods of time despite antiretroviral therapy. There has been controversy on whether low level viral replication is occurring at sanctuary sites periodically reseeding infected cells into the latent reservoir to account its durability. To study viral evolution in a physiologically relevant population of latent viruses, we repeatedly performed virus outgrowth assays on a stably treated HIV positive patient over two years and sequenced the reactivated latent viruses. We sought evidence of increasing sequence pairwise distances with time as evidence of ongoing viral replication. 64 reactivatable latent viral sequences were obtained over 103 weeks. We did not observe an increase in genetic distance of the sequences with the time elapsed between sampling. No evolution could be discerned in these reactivatable latent viruses. Thus, in this patient, the contribution of low-level replication to the maintenance of the latent reservoir detectable in the blood compartment is limited.

Description

Keywords

CD4-Positive T-Lymphocytes, Evolution, Molecular, HIV Infections, HIV-1, Humans, Male, Middle Aged, Viral Load, Virus Latency, Virus Replication

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/M003515/1)
Academy of Medical Sciences (unknown)
NIHR Clinical Research Network Eastern (via Cambridge University Hospitals NHS Foundation Trust (CUH)) (CRN Core Allocation 2014/15 Di)
British HIV Association (BHIVA) (unknown)
Medical Research Council (MR/N02043X/1)