HIV reservoirs: the new frontier

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Current antiretroviral therapies effectively suppress HIV viremia but fail to eliminate persistent viral reservoirs.
• HIV establishes infection in various cell types through multiple mechanisms, creating sanctuaries like the brain.
• CD4+ T-cells harbor the largest pool of persistently infected cells, making them a key focus for research.

Purpose of the Study:

• To review the challenges and advancements in understanding and modeling HIV persistence.
• To highlight the limitations of current in vitro models in recapitulating complex in vivo HIV-cell interactions.
• To emphasize the need for validating model findings with clinical samples for effective HIV eradication strategies.

Main Methods:

• Review of existing literature on HIV persistence and in vitro modeling.
• Analysis of challenges in developing therapies targeting HIV reservoirs.
• Discussion of the complexities of HIV-cell interactions in different cellular reservoirs and anatomical sites.

Main Results:

• In vitro models of HIV persistence, particularly in CD4+ T-cells, have been developed to study viral reservoirs.
• These models offer advantages but share limitations in fully replicating in vivo virus-cell dynamics.
• Conflicting results from different models necessitate validation with clinical samples.

Conclusions:

• Understanding the complex mechanisms of HIV persistence in various cellular reservoirs is crucial for developing eradication therapies.
• In vitro models are valuable but require careful interpretation and validation against clinical data.
• Addressing limitations in current models and validating findings are essential steps toward designing effective HIV eradication strategies.