Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure

• Published in: Viruses 2023-12, Vol.15 (12), p.2435
• Main Authors: Duggan, Natasha N, Dragic, Tatjana, Chanda, Sumit K, Pache, Lars
• Format: Article
• Language: English
• Subjects: Antiretroviral therapy; Antiviral agents; block and lock; Care and treatment; CD4 antigen; CD4-Positive T-Lymphocytes; Chronic illnesses; Clinical trials; Dosage and administration; Epigenetics; Gene expression; Gene regulation; HIV; HIV infection; HIV Infections; HIV patients; HIV Seropositivity; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immune response; Infections; Kinases; Latency; latency reversal; Latent infection; LRA; Lymphocytes; Lymphocytes T; Metabolism; Mortality; Prevention; Proteins; Recovery of function; Risk factors; RNA polymerase; shock and kill; viral latency; Virus Activation; Virus Latency; Virus Replication
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15122435

Antiretroviral therapy (ART) has brought the HIV/AIDS epidemic under control, but a curative strategy for viral eradication is still needed. The cessation of ART results in rapid viral rebound from latently infected CD4+ T cells, showing that control of viral replication alone does not fully restore immune function, nor does it eradicate viral reservoirs. With a better understanding of factors and mechanisms that promote viral latency, current approaches are primarily focused on the permanent silencing of latently infected cells ("block and lock") or reactivating HIV-1 gene expression in latently infected cells, in combination with immune restoration strategies to eliminate HIV infected cells from the host ("shock and kill"). In this review, we provide a summary of the current, most promising approaches for HIV-1 cure strategies, including an analysis of both latency-promoting agents (LPA) and latency-reversing agents (LRA) that have shown promise in vitro, ex vivo, and in human clinical trials to reduce the HIV-1 reservoir.