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Establishment and stability of the latent HIV-1 DNA reservoir

Authors :
Johanna Brodin
Fabio Zanini
Lina Thebo
Christa Lanz
Göran Bratt
Richard A Neher
Jan Albert
Source :
eLife, Vol 5 (2016)
Publication Year :
2016
Publisher :
eLife Sciences Publications Ltd, 2016.

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.

Details

Language :
English
ISSN :
2050084X
Volume :
5
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.4d3fe22014e42989b5a8ca6b8bd9e1c
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.18889