Novel Strategies to Identify and Eliminate Latent HIV Cells

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 2700

Special Issue Editor


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Guest Editor
CHUV, Divison of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland
Interests: HIV; HIV reservoir; quantification of HIV DNA and RNA; single cells analysis; HIV reactivation; HIV cure; HIV vaccines

Special Issue Information

Dear Colleagues,

Due to the availability of antiretroviral therapy (ART), HIV-1 infection has transitioned into a chronic condition. ART effectively suppresses plasma viral loads to undetectable levels, thereby preventing the progression to AIDS. However, the virus remains latent and persists in the body, posing a significant challenge to achieving a cure. If ART is discontinued, the virus rebounds, necessitating lifelong medication for those affected.

Cutting-edge technologies have dramatically enhanced our understanding of HIV-1 infection at the single-cell level (for example, HIVseq, FINDseq, viral ASAPseq), facilitating remarkable progress in the field.

Despite numerous setbacks in the quest for a cure, novel therapeutic approaches have already reached the clinical trial stage, and new strategies are continually being proposed and implemented (for example CRISPR, targeted lipid nanoparticles, broadly neutralizing antibodies, AZD5582, trimeric Env, TLR7 agonist, anti-HIV CAR-T and/or a combination of them).

The objective of this Special Issue of Viruses is to examine and discuss recent advancements in the analysis of HIV-1 viral infection at the single-cell level, as well as the latest ongoing efforts in developing new cure strategies. 

Dr. Francesco Andrea Procopio
Guest Editor

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Keywords

  • HIV
  • HIV-1 infection
  • antiretroviral therapy (ART)
  • HIV single cell analysis

  • HIV reservoir
  • HIV cure

 

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Published Papers (1 paper)

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Research

20 pages, 5726 KiB  
Article
Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors
by Hasset Tibebe, Dacia Marquez, Aidan McGraw, Sophia Gagliardi, Cailyn Sullivan, Grace Hillmer, Kedhar Narayan, Coco Izumi, Adleigh Keating and Taisuke Izumi
Viruses 2025, 17(3), 400; https://doi.org/10.3390/v17030400 - 12 Mar 2025
Viewed by 2010
Abstract
The “Kick and Kill” strategy, which aims to reactivate latent HIV reservoirs and facilitate the clearance of reactivated HIV-infected cells, has yet to achieve a functional cure due to the limited efficacy of current latency reversal agents. This study evaluates the combination efficacy [...] Read more.
The “Kick and Kill” strategy, which aims to reactivate latent HIV reservoirs and facilitate the clearance of reactivated HIV-infected cells, has yet to achieve a functional cure due to the limited efficacy of current latency reversal agents. This study evaluates the combination efficacy of histone deacetylase (HDAC) inhibitor with poly(ADP-ribose) polymerase (PARP) inhibitor in latency reversal and immune-mediated clearance. Latently infected J-Lat cells and dual-fluorescent HIV-infected primary CD4 T cells were treated with the HDAC inhibitor (vorinostat) and one of four PARP inhibitors (olaparib, rucaparib, niraparib, or talazoparib). PARP inhibitors, when administered alone, showed no latency reversal activity. However, when combined with vorinostat, their efficacy increased threefold compared to vorinostat alone. This effect was mediated by the inhibition of tankyrase, a PARP superfamily member, which modulates the Hippo signaling pathway. In HIVGR670-infected primary cells, the combination reduced the reservoir size by 67%. In addition, talazoparib alone significantly reduced actively infected cells by 50%. Talazoparib-treated peripheral blood mononuclear cells co-cultured with K562 cells demonstrated enhanced NK-cell-mediated cytotoxicity, with a 10% reduction in K562 cell viability. These findings demonstrate that combining HDAC and PARP inhibitors augments latency reversal and reservoir reduction. With both the HDAC inhibitors and PARP inhibitors used in this study approved by the FDA for cancer treatment, this combination therapy holds strong potential for rapid clinical integration, contingent upon the confirmation of efficacy and safety in ongoing in vivo studies. Full article
(This article belongs to the Special Issue Novel Strategies to Identify and Eliminate Latent HIV Cells)
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