Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension

@article{Lewis2011GoldDA,
  title={Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension},
  author={Mark G. Lewis and Sandrina DaFonseca and Nicolas Chomont and Anna T. Sigma-Tau Ind. Farm. Reun. SpA Palamara and Maria Tardugno and Antonello Mai and Matt Collins and Wendeline Wagner and Jake Yalley-Ogunro and Jack Greenhouse and Barbara Chirullo and Sandro Norelli and Enrico Garaci and Andrea Savarino},
  journal={AIDS},
  year={2011},
  volume={25},
  pages={1347–1356}
}
Objectives:A small pool of long-lived memory CD4+ T cells harboring the retroviral genome is one main obstacle to HIV eradication. We tested the impact of the gold compound, auranofin, on phenotype and viability of CD4+ T cells in vitro, and on persistence of lentiviral reservoir cells in vivo. Design:In-vitro and in-vivo study. The pro-differentiating effect of auranofin was investigated in human primary CD4+ T cells, and its capacity to deplete the viral DNA (vDNA) reservoir was tested in a… Expand
A Highly Intensified ART Regimen Induces Long-Term Viral Suppression and Restriction of the Viral Reservoir in a Simian AIDS Model
TLDR
This work shows, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing potential cures for AIDS. Expand
Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
TLDR
The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current “ART for life” plight. Expand
HIV-1 Latency: An Update of Molecular Mechanisms and Therapeutic Strategies
TLDR
This review will briefly summarize the more recent advances in the elucidation of mechanisms that regulates the establishment/maintenance of latency and therapeutic strategies currently under evaluation in order to eradicate HIV persistence. Expand
Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy
TLDR
The results showed that Plasmodium infection reduced both the replication-competent virus pool in resting CD4+ T cells and the integrated virus DNA (iDNA) load in peripheral blood mononuclear cells in the monkeys. Expand
A candidate anti-HIV reservoir compound, auranofin, exerts a selective ‘anti-memory' effect by exploiting the baseline oxidative status of lymphocytes
TLDR
It is shown that TCM and TTM lymphocytes have lower baseline antioxidant defenses as compared with their naive counterpart, and AF selectively targets the TCM/TTM lymphocyte subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell death pathways. Expand
The development of immune-modulating compounds to disrupt HIV latency.
TLDR
This review will focus on the potential use of small molecules in the "shock and kill" strategy, the molecular basis for their action and the potential advantages of their immune-modulating activities. Expand
Identification of novel cellular factors involved in HIV-1 latency
TLDR
Auranofin was identified to enhance reversal of latency when applied in combination with all tested LRAs, i.e. TNFα, prostratin, SAHA or sodium butyrate in J-Lat cells and in combination in U1 cells, and diminazene was identify to also have an effect on latency reversal. Expand
Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: results from a randomized clinical trial.
TLDR
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, and it is found that aurenofin treatment was well tolerated. Expand
Therapeutics for HIV-1 reactivation from latency.
TLDR
Proposed eradication strategies involve reactivation of the latent reservoir upon induction of viral transcription followed by the elimination of reactivated virus-producing cells by viral cytopathic effect or host immune response. Expand
Human Immunodeficiency Virus Playing Hide-and-Seek: Understanding the TFH Cell Reservoir and Proposing Strategies to Overcome the Follicle Sanctuary
TLDR
This review focuses on a recently discovered HIV reservoir in a subset of CD4+ T cells called the follicular helper T (TFH) cells, the potential mechanisms for the emergence of reservoir in TFH cells, and the strategies to target and eliminate this viral reservoir. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 50 REFERENCES
Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy
TLDR
Raltegravir is capable of inhibiting SIVmac251 replication both in tissue culture and in vivo, which may help to develop effective ART regimens for the simian AIDS model entirely based on drugs adopted for treatment in humans. Expand
Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy.
  • T. Chun, L. Stuyver, +6 authors A. Fauci
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
Highly purified CD4+ T cells from patients receiving HAART with an average treatment time of 10 months and with undetectable plasma viremia carried integrated proviral DNA and were capable of producing infectious virus upon cellular activation in vitro, suggesting persistent active virus replication in vivo. Expand
Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy
TLDR
Targeting infected M/M with fludarabine-loaded RBC at a time when PMPA is suppressing viral replication taking place in activated CD4+ T cells suggests a reduction in the size of SIV reservoirs during chronic HIV infection. Expand
Can HIV be Cured? Mechanisms of HIV persistence and strategies to combat it.
  • D. Hamer
  • Medicine
  • Current HIV research
  • 2004
TLDR
A review of recent studies on the ability of HIV to persist despite highly active antiretroviral therapy and immune stimulation suggests that achieving stable remission will require four developments in basic and clinical science. Expand
HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
TLDR
The results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and drugs that interfere with the self renewal and persistence of proliferating memory T cells. Expand
Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy.
TLDR
In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes, and generally did not show mutations associated with resistance to the relevant antiretroviral drugs. Expand
Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies
TLDR
The current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency are reviewed and the potential of new therapeutic strategies based on this understanding of latency are highlighted. Expand
A randomized controlled trial of HIV therapeutic vaccination using ALVAC with or without Remune
TLDR
Although ALVAC with or without Remune did not lower the viral load set-point, it tended to delay viral load rebound and was associated with a greater time to meet preset criteria to restart ART. Expand
Central memory CD4 T cells are the predominant cell subset resistant to anergy in SIV disease resistant sooty mangabeys
TLDR
The maintenance of recall responses in sooty mangabeys is associated with the resistance of central memory CD4 T cells to the induction of anergy which may represent an important mechanism underlying SIV disease resistance in this species. Expand
Relationship between the size of the human immunodeficiency virus type 1 (HIV-1) reservoir in peripheral blood CD4+ T cells and CD4+:CD8+ T cell ratios in aviremic HIV-1-infected individuals receiving long-term highly active antiretroviral therapy.
TLDR
Persistent, low-level, ongoing viral replication, although not sufficient to maintain HIV-1-specific CTL responses, may explain, in part, why normalization of the CD4+:CD8+ T cell ratio is not achieved in some infected individuals successfully treated with HAART. Expand
...
1
2
3
4
5
...