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A Canadian Survey of Research on HIV-1 Latency-Where Are We Now and Where Are We Heading?
Ana Luiza Abdalla1,2, Gabriel Guajardo-Contreras1,3, Andrew J Mouland1,2,3
1HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Insights
Current HIV-1 treatments suppress the virus but don't eliminate latent reservoirs. Research is exploring how HIV-1 establishes latency and developing latency-reversing agents (LRAs) to target these reservoirs for a potential cure.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Over 40 million people globally live with HIV-1.
- Current combination antiretroviral therapy (cART) inhibits viral replication but cannot eliminate latent HIV-1 reservoirs.
- Latent HIV-1 infected cells serve as viral reservoirs, leading to rebound viremia upon cART interruption.
Purpose of the Study:
- To provide a comprehensive overview of HIV-1 latency.
- To highlight Canadian research contributions in understanding and targeting HIV-1 latency.
- To inform curative strategies by reviewing the establishment and maintenance of latent HIV-1 infection.
Main Methods:
- Review of research on the establishment and maintenance of HIV-1 latency.
- Analysis of methodologies for identifying and characterizing latently infected cells.
- Evaluation of the discovery and assessment of latency-reversing agents (LRAs).
- Summary of clinical trials investigating LRA efficacy in people living with HIV (PLWH).
Main Results:
- Latent HIV-1 reservoirs persist despite effective cART.
- LRAs have shown success in reactivating HIV-1 expression in vitro.
- Canadian research has advanced the understanding of HIV-1 latency mechanisms.
- Various methodologies have been developed to characterize latent reservoirs.
Conclusions:
- Understanding HIV-1 latency is crucial for developing curative strategies.
- Targeting latent reservoirs with LRAs is a promising therapeutic approach.
- Continued research, particularly in Canadian labs, is vital for advancing HIV-1 cure efforts.
- Clinical trials are essential to evaluate the safety and efficacy of LRAs in PLWH.
Abstract:
Worldwide, almost 40 million people are currently living with HIV-1. The implementation of cART inhibits HIV-1 replication and reduces viremia but fails to eliminate HIV-1 from latently infected cells. These cells are considered viral reservoirs from which HIV-1 rebounds if cART is interrupted. Several efforts have been made to identify these cells and their niches. There has been little success in diminishing the pool of latently infected cells, underscoring the urgency to continue efforts to fully understand how HIV-1 establishes and maintains a latent state. Reactivating HIV-1 expression in these cells using latency-reversing agents (LRAs) has been successful, but only in vitro. This review aims to provide a broad view of HIV-1 latency, highlighting Canadian contributions toward these aims. We will summarize the research efforts conducted in Canadian labs to understand the establishment of latently infected cells and how this informs curative strategies, by reviewing how HIV latency is established, which cells are latently infected, what methodologies have been developed to characterize them, how new compounds are discovered and evaluated as potential LRAs, and what clinical trials aim to reverse latency in people living with HIV (PLWH).
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