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

Hoi Ping Mok,Mark R Wills,Andrew M L Lever,Jack C Hirst,Axel Fun,Mikaila Bandara,Nicholas J Norton

doi:10.1038/s41598-018-20682-w

Hoi Ping Mok, Mark R Wills + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-20682-w

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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.

Highlights

The principal barrier to the eradication of HIV is a reservoir of latently infected cells that serves as a source of viral recrudescence upon cessation of antiretroviral therapy (ART)
The participant gave written informed consent and this study was approved by the National Health
The HIV positive patient involved in this study had been stably treated with ART for over 7 years

Summary

Introduction

The principal barrier to the eradication of HIV is a reservoir of latently infected cells that serves as a source of viral recrudescence upon cessation of antiretroviral therapy (ART). The most widely studied latent virus pool is that found in circulating resting CD4+ T cells This reservoir is stable despite years of effective ART; the mechanisms by which it is maintained are incompletely understood. We report a case study conducted over 103 weeks on an HIV positive patient diagnosed with haemochromatosis, the treatment for which demanded frequent large volume venesection. This offered an opportunity to study the evolution and clonality of replication competent latent viruses in the blood compartment. But consistent with previous longitudinal studies, over this two-year period no ongoing evolution was observed in this rigorously defined, physiologically relevant latent HIV reservoir

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