Current views on HIV-1 latency, persistence, and cure.

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Human Immunodeficiency Virus type 1 (HIV-1) establishes a persistent infection by hiding in latent reservoirs, rendering it incurable with current therapies.
• Lifelong antiretroviral therapy is required to suppress active viral replication, but does not eliminate the latent reservoir.
• Understanding the mechanisms of HIV-1 latency and low-level replication is crucial for developing curative strategies.

Purpose of the Study:

• To review and summarize current scientific understanding and therapeutic approaches aimed at achieving a functional or sterilizing cure for HIV-1 infection.
• To highlight the challenges posed by the latent HIV-1 reservoir and ongoing low-level replication.
• To discuss novel strategies targeting HIV-1 latency, reactivation, and host resistance.

Main Methods:

• Review of existing literature on HIV-1 latency, viral reservoirs, and therapeutic interventions.
• Analysis of current and emerging strategies for HIV-1 cure, including 'shock and kill', gene therapy, gene editing, and stem cell transplantation.
• Synthesis of concepts underlying the establishment, maintenance, and reactivation of HIV-1 latency.

Main Results:

• The latent reservoir of HIV-1 is a primary barrier to cure, evading immune surveillance and current treatments.
• Low-level HIV-1 replication persists despite suppressive therapy, driven by unidentified mechanisms.
• Multiple innovative approaches are under investigation, including reactivating latent virus and generating HIV-1 resistant cells.

Conclusions:

• Achieving a functional or sterilizing cure for HIV-1 requires targeting the latent reservoir and persistent low-level replication.
• Strategies like 'shock and kill', gene therapy, and stem cell transplantation show promise but face significant challenges.
• Continued research into the fundamental biology of HIV-1 latency is essential for advancing curative therapies.