The Current Status of Latency Reversing Agents for HIV-1 Remission

Annual Review of Virology, Journal Year: 2021, Volume and Issue: 8(1), P. 491 - 514

Published: Sept. 29, 2021

Combinatory antiretroviral therapy (cART) reduces human immunodeficiency virus type 1 (HIV-1) replication but is not curative because cART interruption almost invariably leads to a rapid rebound of viremia due the persistence stable HIV-1-infected cellular reservoirs. These reservoirs are mainly composed CD4+ T cells harboring replication-competent latent proviruses. A broadly explored approach reduce HIV-1 reservoir size, shock and kill strategy, consists reactivating gene expression from latently infected (the shock), followed by killing virus-producing kill). Based on improved understanding multiple molecular mechanisms controlling latency, distinct classes latency reversing agents (LRAs) have been studied for their efficiency reactivate viral in vitro ex vivo cell models. Here, we provide an up-to-date review these different mechanistic LRAs discuss optimizations strategy combining several simultaneously or sequentially.

Language: Английский

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Exosome-mediated stable epigenetic repression of HIV-1

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 20, 2021

Abstract Human Immunodeficiency Virus (HIV-1) produces a persistent latent infection. Control of HIV-1 using combination antiretroviral therapy (cART) comes at the cost life-shortening side effects and development drug-resistant HIV-1. An ideal safer should be deliverable in vivo target stable epigenetic repression virus, inducing “block lock” virus expression. Towards this goal, we developed an promoter-targeting Zinc Finger Protein (ZFP-362) fused to active domains DNA methyltransferase 3 A induce long-term Cells were engineered produce exosomes packaged with RNAs encoding repressor protein. We find here that loaded anti-HIV-1 suppress expression suppression is mechanistically driven by methylation humanized NSG mouse models. The observations presented pave way for exosome-mediated systemic delivery platform therapeutic cargo epigenetically repress

Language: Английский

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The reservoir of latent HIV

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: July 28, 2022

The persistence of latent reservoir the human immunodeficiency virus (HIV) is currently major challenge in curing HIV infection. After infects body, unable to be recognized by body’s immune system. Currently, widely adopted antiretroviral therapy (ART) also unble eliminate it, thus hindering progress treatment. This review discusses existence vault for treatment, its formation and factors affecting formation, cell, tissue localization, methods detection removing reservoir, provide a comprehensive understanding vault, order assist future research play potential role achieving

Language: Английский

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CRISPR/Cas9: a tool to eradicate HIV-1

AIDS Research and Therapy, Journal Year: 2022, Volume and Issue: 19(1)

Published: Dec. 1, 2022

Abstract The development of antiretroviral therapy (ART) has been effective in suppressing HIV replication. However, severe drug toxicities due to the and its failure targeting integrated proviral genome have led introduction a new paradigm gene-based therapies. With inhibition high precision, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) or CRISPR/Cas9 emerged as an editing tool last decade. Mediated by guide RNAs (gRNAs), Cas9 endonuclease acts like genetic scissors that can modify specific target sites. this concept, used HIV-1 both vitro well vivo studies including non-human primates. CRISPR also tested for latent modulating transcription with help specialized mutant. Overcoming limitations current therapy, potential become primary eradicating infection. In review, we summarize recent advancements genome, challenges future prospects.

Language: Английский

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HIV Persistence, Latency, and Cure Approaches: Where Are We Now?

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1163 - 1163

Published: July 19, 2024

The latent reservoir remains a major roadblock to curing human immunodeficiency virus (HIV) infection. Currently available antiretroviral therapy (ART) can suppress active HIV replication, reduce viral loads undetectable levels, and halt disease progression. However, drugs are unable target cells that latently infected with HIV, which seed rebound if ART is stopped. Consequently, focus of the field study develop safe effective methods eliminate it. Here, we provide an overview mechanisms governing establishment maintenance latency, key challenges posed by reservoirs, small animal models utilized contemporary cure approaches. We also discuss ongoing efforts apply these approaches in combination, goal achieving safe, effective, scalable for be extended tens millions people worldwide.

Language: Английский

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A critical assessment of male HIV/AIDS patients’ satisfaction with antiretroviral therapy and its implications for sustainable development in Sub-Saharan Africa

Journal of Health Organization and Management, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Purpose The emergence of unique and destructive viruses, such as COVID-19, has claimed lives, disrupted health systems diverted resources from addressing the needs male HIV/AIDS patients in context antiretroviral therapy other HIV/AIDS-related issues. This study aims to assess patients’ satisfaction with its implications for sustainable development Sub-Saharan Africa. Design/methodology/approach Satisfaction, word-of-mouth, trust revisit intention were variables research model. A quantitative method was utilized. Data collected 400 who received medical attention hospitals Gombe State, Nigeria, utilizing convenience sampling method. SmartPLS used data analysis. Findings results show that a positive impact on trust, word-of-mouth intention. Furthermore, had significant intentions. Word-of-mouth played mediating role relationship between Trust an insignificant Additionally, effect Healthcare organisations should prioritise patient because it influences their likelihood returning. Addressing HIV can significantly enhance overall healthcare experience, which would lead them spread word mouth. Research limitations/implications administrators make top priority provide superior services match or exceed expectations. focused gender. Also, empirical is carried out public hospitals; however, there are some differences types terms factors affect revisits. We employed cross-sectional study. As result, we recommend expanding into longitudinal study, allows researcher validate causal mechanism obtain more generalizable. Practical managers actively encourage reviews recommendations. Setting up record distribute success stories improve hospital’s reputation attract new patients. Increased advertising naturally result encouraging encounters outcomes. establish channels sharing information regarding therapies, procedures support transparent easy obtain. Patients’ intentions return follow-up appointments be favourably influenced by education value ongoing care. Social Male satisfied care have tendency professionals more, promotes enhanced therapeutic outcomes greater compliance treatment regimens. Positive comments those condition also reduce stigma motivate community members seek treatment, fostering supportive environment living HIV/AIDS. emphasises how important providers stronger, empathy connections, could contribute decreasing disparities. Originality/value investigates highlights WOM mediate this relationship.

Language: Английский

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HIV in the Brain: Identifying Viral Reservoirs and Addressing the Challenges of an HIV Cure

Vaccines, Journal Year: 2021, Volume and Issue: 9(8), P. 867 - 867

Published: Aug. 5, 2021

Advances in antiretroviral therapy have prolonged the life of people living with HIV and diminished level virus these individuals. Yet, quickly rebounds after disruption and/or cessation treatment due to significant cellular anatomical reservoirs for HIV, which underscores challenge cure strategies. The central nervous system (CNS), particular, is seeded within 1–2 weeks infection a reservoir HIV. In this review, we address paradigm CNS relevant cell types, including astrocytes microglia, that been shown harbor viral even treatment. focus on developmental aspects microglia lead their susceptibility infection, how propagates among cells. We also challenges measuring latent reservoir, advances detection assays, curative strategies evolved regard reservoir. Current still require optimization reduce or eliminate may contribute levels neuroinflammation cognitive decline. With mind, brain should remain prominent when assessing options overall burden clinic, especially context HIV-associated neurocognitive disorders (HAND).

Language: Английский

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HIV persistence: silence or resistance?

Current Opinion in Virology, Journal Year: 2023, Volume and Issue: 59, P. 101301 - 101301

Published: Feb. 17, 2023

Despite decades of suppressive antiretroviral therapy, human immunodeficiency virus (HIV) reservoirs in infected individuals persist and fuel viral rebound once therapy is interrupted. The persistence the main obstacle to achieving HIV eradication or a long-term remission. last decade has seen profound change our understanding mechanisms behind persistence, which appears be much more complex than originally assumed. In addition transcriptionally silent proviruses stable latent reservoir that invisible immune system, increasingly recognized by resistance clearance, play surprisingly prominent role shaping reservoir. this review, we discuss some emerging insights into as well their implications for development strategies towards an cure.

Language: Английский

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Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation

Phytomedicine, Journal Year: 2023, Volume and Issue: 116, P. 154855 - 154855

Published: May 3, 2023

Language: Английский

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HIV Reservoirs and Treatment Strategies toward Curing HIV Infection

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2621 - 2621

Published: Feb. 23, 2024

Combination antiretroviral therapy (cART) has significantly improved the prognosis of individuals living with human immunodeficiency virus (HIV). Acquired syndrome transformed from a fatal disease to treatable chronic infection. Currently, effective and safe anti-HIV drugs are available. Although cART can reduce viral production in body patient below detection limit, it cannot eliminate HIV provirus integrated into host cell genome; hence, will be produced again after discontinuation. Therefore, research cure (or remission) for been widely conducted. In this review, we focus on drug development targeting cells latently infected assess progress including our current studies, particularly terms “Shock Kill”, “Block Lock” strategies.

Language: Английский

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