Defining total-body AIDS-virus burden with implications for curative strategies
| Autor: | Gregory J. Beilman, Jeffrey D. Lifson, Francis Ssali, Jordan Schoephoerster, Steven G. Deeks, Samuel P. Callisto, Claire Deleage, Courtney V. Fletcher, Jacob D. Estes, Jacob Jasurda, Torfi Hoskuldsson, Thomas E. Schmidt, Joseph M. McCune, Jared Schuster, Michael Hafertepe, Alexander Khoruts, Cissy Kityo, Gregory Q. Del Prete, Thomas Reimann, Peter J. Southern, Timothy W. Schacker, Paul A. Luciw, Ashley T. Haase, Katherine Perkey, Krystelle Nganou Makamdop, Jodi Anderson, Hope Pearson, Jeffrey G. Chipman, Liang Shang, Louise A. Swainson, Daniel C. Douek, Stephen W. Wietgrefe |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug Anti-HIV Agents Lymphoid Tissue media_common.quotation_subject 030106 microbiology HIV Infections Article General Biochemistry Genetics and Molecular Biology Virus Persistence (computer science) 03 medical and health sciences Acquired immunodeficiency syndrome (AIDS) medicine Humans media_common business.industry HIV RNA General Medicine Viral Load medicine.disease Virology 030104 developmental biology Lymphatic system Viral replication DNA Viral Immunology RNA Viral business Viral load |
| Zdroj: | Nature Medicine. 23:1271-1276 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | In the quest for a functional cure or eradication of HIV infection, we need to know how large the reservoirs are from which infection rebounds when treatment is interrupted. To that end, we quantified SIV and HIV tissue burdens in tissues of infected non-human primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs harbor more than 98 percent of the SIV RNA+ and DNA+ cells. While ART substantially reduced their numbers, vRNA+ cells were still detectable and their persistence was associated with relatively low drug concentrations in LT compared to peripheral blood. Prolonged ART also reduced the level of SIV and HIV-DNA+ cells, but the estimated size of the residual tissue burden of 108 vDNA+ cells that potentially harbor replication competent proviruses, along with the evidence for continuing virus production in LT despite ART, identify two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore the challenges in developing “HIV cure” strategies that target multiple sources of virus production. |
| Databáze: | OpenAIRE |
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