Establishment and stability of the latent HIV-1 DNA reservoir
- Karolinska Institute, Sweden
- Stanford University, United States
- Max Planck Institute for Developmental Biology, Germany
- Stockholm South General Hospital, Sweden
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, 2015) we documented HIV-1 evolution 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.
Data availability
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Establishment and stability of the latent HIV-1 DNA reservoirPublicly available at the EBI European Nucleotide Archive (Accession no: PRJEB13841).
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HIVEVOPublicly available at the EBI European Nucleotide Archive (Accession no: PRJEB9618).
Article and author information
Author details
Funding
European Research Council (Stg. 260686)
- Richard A Neher
Vetenskapsrådet (K2014-57X-09935)
- Jan Albert
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was conducted according to the Declaration of Helsinki. Ethical approval was granted by the Regional Ethical Review board in Stockholm, Sweden (Dnr 2012/505 and 2014/646). Patients participating in the study gave written and oral informed consent to participate.
Copyright
© 2016, Brodin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Establishment and stability of the latent HIV-1 DNA reservoir
eLife 5:e18889.
https://doi.org/10.7554/eLife.18889
