Tools to Quantify and Characterize the Persistent Reservoir in People with HIV-1: Focus on Non-B Subtypes

Area of Science:

• Virology
• Immunology
• Global Health

Background:

• Human immunodeficiency virus type 1 (HIV-1) remains a significant global health challenge.
• Combination antiretroviral therapy (cART) effectively controls HIV-1 replication, changing the disease course to chronic.
• A persistent HIV-1 reservoir can cause viral rebound even with undetectable viremia during cART.

Purpose of the Study:

• To review and discuss existing tools for quantifying and characterizing the persistent HIV-1 reservoir.
• To explore the limitations of current tools, particularly for non-B HIV-1 subtypes.
• To advocate for standardized, accessible assays for reservoir analysis across all HIV-1 subtypes.

Main Methods:

• Review of quantitative viral outgrowth assays (qVOA) and molecular assays (DNA, RNA, protein).
• Analysis of tool applicability and limitations for HIV-1 subtype B versus non-B subtypes.
• Discussion of adaptations and standardization needs for global accessibility.

Main Results:

• Existing reservoir quantitation tools are primarily developed for HIV-1 subtype B.
• Non-B subtypes, prevalent globally, present challenges for current reservoir measurement techniques.
• Adaptations and validation are necessary to accurately assess reservoirs in non-B subtype infections.

Conclusions:

• Standardized, well-validated, and globally accessible tools are crucial for characterizing HIV-1 reservoir dynamics.
• Subtype-specific reservoir analysis is essential for understanding viral rebound and informing treatment strategies.
• Wider accessibility of these tests will enable robust conclusions on subtype-specific reservoir dynamics.