Assessing proviral competence: current approaches to evaluate HIV-1 persistence

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Antiretroviral therapy (ART) suppresses HIV-1 but does not eliminate persistent viral reservoirs.
• These reservoirs are the primary barrier to HIV-1 eradication and long-term remission.
• Monitoring reservoir size is essential for evaluating the efficacy of potential curative strategies.

Purpose of the Study:

• To review recent advancements in assays designed to measure HIV-1 persistence.
• To highlight the advantages and limitations of current and emerging reservoir quantification techniques.
• To provide an overview of methods for assessing viral reservoir size and composition in individuals on ART.

Main Methods:

• Review of various assays for measuring HIV-1 persistence, including viral outgrowth assays, sequencing-based assays, and methods assessing transcriptional and translational competence.
• Discussion of next-generation reservoir assays incorporating single-cell analysis and integration site characterization.
• Evaluation of techniques for quantifying proviral replication competence, genetic intactness, and viral production.

Main Results:

• Multiple assays have been developed to assess different facets of HIV-1 persistence.
• Recent assays offer enhanced capabilities, including single-cell resolution and integration site analysis.
• These advancements enable more reliable estimation of the HIV-1 reservoir size and its characteristics.

Conclusions:

• No single assay provides a perfect measure of the HIV-1 reservoir.
• Recent technical progress significantly improves the accuracy and comprehensiveness of reservoir size estimation.
• Improved assays are vital for monitoring the effectiveness of interventions aimed at HIV-1 cure or long-term remission.