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Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.
Tram M Ta1, Sajjaf Malik1, Elizabeth M Anderson2
1Department of Biological Sciences, Misher College of Arts and Sciences, University of the Sciences in Philadelphia, Philadelphia, PA, United States.
Frontiers in Microbiology
|May 16, 2022
Summary
Combination antiretroviral therapy (cART) suppresses HIV-1 but lifelong treatment is needed due to latent reservoirs. Research explores mechanisms of HIV persistence and strategies for a functional cure by targeting these reservoirs.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Combination antiretroviral therapy (cART) effectively suppresses HIV-1 replication but necessitates lifelong treatment for people living with HIV (PLWH).
- Increased life expectancy in PLWH on cART is accompanied by a rise in age-related comorbidities, posing significant burdens.
- The persistence of latent HIV reservoirs, established during acute infection, is the primary barrier to a functional HIV cure.
Purpose of the Study:
- To review the current understanding of HIV-1 persistence mechanisms in peripheral and tissue compartments.
- To summarize interdisciplinary strategies aimed at achieving a functional HIV cure.
- To highlight novel approaches for measuring and eliminating HIV reservoirs and inducing immune control.
Main Methods:
- Review of recent scientific literature on HIV-1 latency, persistence, and cure strategies.
- Analysis of host and viral factors contributing to reservoir establishment and maintenance.
- Synthesis of interdisciplinary research findings on reservoir elimination and immune-based therapies.
Main Results:
- HIV reservoirs are established early and can expand clonally within immune cells, primarily memory CD4+ T cells, but also monocytes, macrophages, and dendritic cells.
- HIV latency is regulated by complex molecular mechanisms, including epigenetic control of proviral transcription, RNA processing, and nuclear export.
- Defective proviruses can contribute to immune activation through viral protein expression or production of replication-defective particles.
Conclusions:
- Understanding the multifaceted mechanisms of HIV persistence is crucial for developing effective cure strategies.
- Targeting latent reservoirs and enhancing immune control are key components of interdisciplinary approaches toward a functional HIV cure.
- Novel methods to measure and eliminate infected reservoirs are essential for advancing HIV cure research.
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