title: 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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Brodin
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Fabio
authors.identifier: 0000-0001-7097-8539
authors.initials: F
authors.lastname: Zanini
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Thebo
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Lanz
authors.affiliation: Department of Clinical Science and Education, Stockholm South General Hospital, Stockholm, Sweden.|Venhälsan, Stockholm South General Hospital, Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Bratt
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Richard A
authors.identifier: 0000-0003-2525-1407
authors.initials: RA
authors.lastname: Neher
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.|Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.identifier: 0000-0001-9020-0521
authors.initials: J
authors.lastname: Albert
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017735:Virus Latency
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral
keywords: HIV; cure; evolution; infectious disease; microbiology; virus