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Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
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Persistent HIV-1 replication maintains the tissue reservoir during therapy
Ramon Lorenzo-Redondo1, Helen R Fryer2, Trevor Bedford3
1Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA.
Nature
|January 28, 2016
Summary
Even with undetectable viral load, human immunodeficiency virus type 1 (HIV-1) continues to replicate in lymphoid tissues. This ongoing viral activity and evolution in reservoirs can occur despite potent antiretroviral therapy.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Lymphoid tissue serves as a critical reservoir for human immunodeficiency virus type 1 (HIV-1) established during acute infection.
- This tissue is implicated in viral production, immune complex storage, and long-term viral persistence.
- The efficacy of combination antiretroviral therapy (cART) in fully suppressing viral replication within these reservoirs remains uncertain.
Purpose of the Study:
- To investigate whether HIV-1 replication and evolution persist in lymphoid tissue reservoirs despite undetectable plasma viral RNA levels during cART.
- To develop a spatial and dynamic model to understand persistent viral replication and spread in these reservoirs.
- To elucidate the mechanisms underlying viral evolution and drug resistance development in the context of insufficient drug concentrations.
Main Methods:
- Analysis of viral evolution and trafficking within tissue compartments in patients on cART with undetectable viremia.
- Development and application of a spatial and dynamic model to simulate persistent viral replication and spread.
- Investigation of factors influencing the development of drug resistance under sub-optimal drug concentrations.
Main Results:
- Virus evolution and trafficking between tissue compartments were observed to continue in patients with undetectable blood virus levels.
- A spatial and dynamic model demonstrated persistent viral replication and spread within lymphoid tissue reservoirs.
- The findings suggest that drug resistance may not be inevitable even when drug concentrations are insufficient to completely block replication.
Conclusions:
- HIV-1 can continue to replicate and replenish its reservoir in lymphoid tissues even during potent antiretroviral therapy.
- Persistent viral replication and evolution within reservoirs challenge the assumption of complete viral suppression with cART.
- These findings offer new insights into the complex evolutionary and infection dynamics of HIV-1 within the host during treatment.
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