Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial

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Abstract

Antiretroviral therapy (ART) is typically composed of a combination of three antiretroviral drugs and is the treatment of choice for people with human immunodeficiency virus type 1/acquired immune deficiency syndrome (HIV-1/AIDS). However, it is unable to impact on viral reservoirs, which harbour latent HIV-1 genomes that are able to reignite the infection upon treatment suspension. The aim of this study was to provide an estimate of the safety of the disease-modifying antirheumatic agent auranofin and its impact on the HIV-1 reservoir in humans under intensified ART. For this purpose, an interim analysis was conducted of three of the six arms of the NCT02961829 clinical trial (five patients each) with: no intervention, i.e. continuation of first-line ART; intensified ART (ART + dolutegravir and maraviroc); and intensified ART plus auranofin. Auranofin treatment was found to be well tolerated. No major adverse events were detected apart from a transient decrease in CD4+ T-cell counts at Weeks 8 and 12. Auranofin decreased total viral DNA in peripheral blood mononuclear cells compared with ART-only regimens at Week 20 (P = 0.036) and induced a decrease in integrated viral DNA as quantified by Alu PCR. Despite the limited number of patient-derived sequences available in this study, phylogenetic analyses of nef sequences support the idea that auranofin may impact on the viral reservoir. [ClinicalTrials.gov ID: NCT02961829].

Original languageEnglish
Pages (from-to)592-600
Number of pages9
JournalInternational Journal of Antimicrobial Agents
Volume54
Issue number5
DOIs
Publication statusPublished - Nov 2019

Bibliographical note

Copyright © 2019 Elsevier Ltd. All rights reserved.

Keywords

  • Antiretroviral Therapy, Highly Active
  • Antirheumatic Agents/therapeutic use
  • Auranofin/therapeutic use
  • CD4 Lymphocyte Count
  • DNA, Viral/drug effects
  • HIV Fusion Inhibitors/therapeutic use
  • HIV Infections/drug therapy
  • HIV Integrase Inhibitors/therapeutic use
  • HIV-1/drug effects
  • Heterocyclic Compounds, 3-Ring/therapeutic use
  • Humans
  • Maraviroc/therapeutic use
  • Oxazines
  • Piperazines
  • Proviruses/drug effects
  • Pyridones
  • Virus Latency/drug effects

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