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Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy

Gladstone Institute of Virology and Immunology, Departments of Medicine, Microbiology & Immunology, University of California, San Francisco, CA 94158, USA
*
Author to whom correspondence should be addressed.
Current address: Weill Cornell Medicine, New York, NY 10021, USA.
Viruses 2020, 12(2), 188; https://doi.org/10.3390/v12020188
Received: 11 January 2020 / Revised: 5 February 2020 / Accepted: 5 February 2020 / Published: 8 February 2020
(This article belongs to the Special Issue HIV-1 Latency: Regulation and Reversal)
Human immunodeficiency virus (HIV-1) indefinitely persists, despite effective antiretroviral therapy (ART), within a small pool of latently infected cells. These cells often display markers of immunologic memory and harbor both replication-competent and -incompetent proviruses at approximately a 1:100 ratio. Although complete HIV eradication is a highly desirable goal, this likely represents a bridge too far for our current and foreseeable technologies. A more tractable goal involves engineering a sustained viral remission in the absence of ART––a “functional cure.” In this setting, HIV remains detectable during remission, but the size of the reservoir is small and the residual virus is effectively controlled by an engineered immune response or other intervention. Biological precedence for such an approach is found in the post-treatment controllers (PTCs), a rare group of HIV-infected individuals who, following ART withdrawal, do not experience viral rebound. PTCs are characterized by a small reservoir, greatly reduced inflammation, and the presence of a poorly understood immune response that limits viral rebound. Our goal is to devise a safe and effective means for replicating durable post-treatment control on a global scale. This requires devising methods to reduce the size of the reservoir and to control replication of this residual virus. In the following sections, we will review many of the approaches and tools that likely will be important for implementing such a “reduce and control” strategy and for achieving a PTC-like sustained HIV remission in the absence of ART. View Full-Text
Keywords: HIV; cure; block and lock; shock and kill; genome editing; reduce and control HIV; cure; block and lock; shock and kill; genome editing; reduce and control
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MDPI and ACS Style

Schwarzer, R.; Gramatica, A.; Greene, W.C. Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy. Viruses 2020, 12, 188. https://doi.org/10.3390/v12020188

AMA Style

Schwarzer R, Gramatica A, Greene WC. Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy. Viruses. 2020; 12(2):188. https://doi.org/10.3390/v12020188

Chicago/Turabian Style

Schwarzer, Roland; Gramatica, Andrea; Greene, Warner C. 2020. "Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy" Viruses 12, no. 2: 188. https://doi.org/10.3390/v12020188

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Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

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