Establishment and stability of the latent HIV-1 DNA reservoir.

Abstract:

:HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini et al, 2015) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3-18 years of suppressive ART. A median of 14% (range 0-42%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.

journal_name

Elife

journal_title

eLife

authors

Brodin J,Zanini F,Thebo L,Lanz C,Bratt G,Neher RA,Albert J

doi

10.7554/eLife.18889

subject

Has Abstract

pub_date

2016-11-15 00:00:00

issn

2050-084X

journal_volume

5

pub_type

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