New latency-promoting agents for a block-and-lock functional cure strategy.

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Antiretroviral therapy (ART) manages HIV-1 infection but does not eliminate latent reservoirs.
• Interruption of ART leads to viral rebound from these latent reservoirs.
• Developing a curative strategy for HIV-1 requires targeting the latent reservoir.

Approach:

• The "block-and-lock" strategy aims for a functional HIV-1 cure.
• This approach "blocks" viral transcription and "locks" the provirus into a deep, treatment-resistant latent state.
• Latency-promoting agents are used to induce transcriptional silencing and epigenetic modifications at the HIV promoter.

Key Points:

• Previous "shock-and-kill" strategies showed limited success in eradicating the latent reservoir.
• The "block-and-lock" approach focuses on inducing and maintaining long-term viral latency.
• Investigating transcriptional and epigenetic regulation is crucial for designing effective latency-promoting agents.

Conclusions:

• The "block-and-lock" strategy offers a promising alternative for achieving a functional HIV-1 cure.
• Further research into latency-promoting agents is essential for optimizing this approach.
• This review discusses latency-promoting agents identified in scientific literature from 2022-2023.