Tracking HIV Rebound following Latency Reversal Using Barcoded HIV

Area of Science:

• Virology
• Immunology
• Drug Discovery

Background:

• Antiretroviral therapy (ART) alone cannot cure HIV due to latent reservoirs.
• Latency-reversing agents (LRAs) aim to reactivate these reservoirs for elimination.
• Novel LRAs are needed to effectively target latent HIV infection.

Purpose of the Study:

• To evaluate a synthetic protein kinase C modulating LRA for its effect on HIV rebound.
• To assess the efficacy of LRAs in combination with ART in a humanized mouse model.
• To investigate the impact of LRA administration on the diversity of rebounding HIV.

Main Methods:

• Utilized a barcoded HIV system for tracking viral evolution.
• Employed a humanized mouse model to simulate HIV infection and treatment.
• Administered a synthetic LRA during ART and monitored viral rebound after treatment cessation.

Main Results:

• LRA administration during ART delayed HIV rebound after treatment interruption.
• Rebounding virus in LRA-treated animals originated from fewer unique viral barcodes compared to controls.
• This suggests LRA treatment reduced the number of actively contributing latent reservoir cells.

Conclusions:

• Barcoded virus approaches are valuable for studying HIV rebound dynamics.
• Synthetic LRAs show potential for reducing the size of the latent HIV reservoir.
• LRAs may represent a viable strategy to enhance HIV cure efforts.