Genetic characterization of the HIV-1 reservoir after Vacc-4x and romidepsin therapy in HIV-1-infected individuals. (24th August 2018)

• Record Type: Journal Article
• Authors: Winckelmann, Anni; Morcilla, Vincent; Shao, Wei; Schleimann, Mariane H.; Hojen, Jesper F.; Schlub, Timothy E.; Benton, Paul W.; Østergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Palmer, Sarah
• Is Part Of: AIDS. Volume 32:Number 13(2018)
• Publication Date: 2018-08-24
• Subjects: HIV cure -- HIV latency -- HIV phylogenetics -- latency reversing agent -- romidepsin -- single-genome sequencing -- therapeutic HIV vaccine; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001861
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text