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

AIDS
Anni WinckelmannSarah Palmer

Abstract

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. 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. 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. 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...Continue Reading

References

Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
Oct 18, 2013·Molecular Biology and Evolution·Koichiro TamuraSudhir Kumar
Nov 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lina JosefssonSarah Palmer
Mar 13, 2014·The Journal of Infectious Diseases·Nancy M ArchinDavid M Margolis
Oct 24, 2014·PloS One·Leslie R CockerhamSteven G Deeks
Sep 18, 2015·PLoS Pathogens·Ole S SøgaardMartin Tolstrup
Feb 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Francesco R SimonettiFrank Maldarelli
Sep 9, 2016·Nature Communications·Kirston BartonSarah Palmer

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Citations

Mar 19, 2019·Current Opinion in HIV and AIDS·Michael J Bale, Mary F Kearney
Nov 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ching-Lan LuMila Jankovic
Sep 10, 2019·Frontiers in Microbiology·Paul W DentonMartin Tolstrup

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Datasets Mentioned

BETA
APP1061681

Methods Mentioned

BETA
PCR

Software Mentioned

Epitope Location Finder
MEGA model finder
Hypermut
Perl
house
ggtree
R
MUSCLE
nlme car
MEGA

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