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

Int J Antimicrob Agents. 2019 Nov;54(5):592-600. doi: 10.1016/j.ijantimicag.2019.08.001. Epub 2019 Aug 5.


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].

Keywords: Antiproliferative agent; Disease-modifying antirheumatic agent; HIV cure; HIV reservoir; Proviral DNA; Viral evolution.

Publication types

  • Randomized Controlled Trial

MeSH terms

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


  • Antirheumatic Agents
  • DNA, Viral
  • HIV Fusion Inhibitors
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Auranofin
  • dolutegravir
  • Maraviroc

Associated data

  • ClinicalTrials.gov/NCT02961829