Lars Jørgen Østergaard

Genetic characterization of the HIV-1 reservoir after Vacc-4x and romidepsin therapy in HIV-1-infected individuals

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Anni Winckelmann, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
  • ,
  • Vincent Morcilla, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
  • ,
  • Wei Shao, Advanced Biomedical Computing Center, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • ,
  • Mariane H Schleimann
  • ,
  • Jesper F Hojen
  • ,
  • Timothy E Schlub, Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
  • ,
  • Paul W Denton
  • ,
  • Lars Østergaard
  • Ole S Søgaard
  • ,
  • Martin Tolstrup
  • Sarah Palmer, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.

OBJECTIVE: Therapeutic HIV-1 immunization followed by latency reversal has been suggested as a strategy to eradicate HIV-1. Here we investigate the phylogenetic composition of the HIV-1 regions targeted by the therapeutic HIV-1 peptide vaccine Vacc-4x in participants in a clinical trial.

DESIGN: Seventeen participants on suppressive antiretroviral therapy were vaccinated with six doses of Vacc-4x followed by three doses of romidepsin. Seven study participants were selected for sequencing analysis. All participants underwent an analytical treatment interruption.

METHODS: Single-genome/proviral sequencing of the p24-RT region was performed to genetically characterize proviral DNA, cell-associated RNA and outgrowth viruses during therapy as well as plasma HIV-1 RNA during an analytical treatment interruption.

RESULTS: There were no changes in cell-associated HIV-1 RNA (P = 0.83) and DNA (P = 0.09) diversity over the course of the study and no difference between cell-associated HIV-1 RNA and DNA diversity (P = 0.32). Only one participant showed signs of potential vaccine-related selection in the rebounding plasma virus. In five of seven participants, we identified human leukocyte antigen-specific cytotoxic T lymphocytes (CTL) epitopes containing nonsilent mutations in 100% of the sequences.

CONCLUSION: We detected no evidence of selective immune pressure reflected in proviral diversity or by occurrence of specific mutation in the vaccine-targeted epitopes. Preexisting CTL epitope mutations may affect the potency of this therapeutic vaccine. This highlights the challenges of developing effective HIV-1 therapeutic vaccines.

Original languageEnglish
JournalAIDS
Volume32
Issue13
Pages (from-to)1793-1802
Number of pages10
ISSN0269-9370
DOIs
Publication statusPublished - 24 Aug 2018

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