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Defining total-body AIDS-virus burden with implications for curative strategies.
Estes, Jacob D; Kityo, Cissy; Ssali, Francis; Swainson, Louise; Makamdop, Krystelle Nganou; Del Prete, Gregory Q; Deeks, Steven G; Luciw, Paul A; Chipman, Jeffrey G; Beilman, Gregory J; Hoskuldsson, Torfi; Khoruts, Alexander; Anderson, Jodi; Deleage, Claire; Jasurda, Jacob; Schmidt, Thomas E; Hafertepe, Michael; Callisto, Samuel P; Pearson, Hope; Reimann, Thomas; Schuster, Jared; Schoephoerster, Jordan; Southern, Peter; Perkey, Katherine; Shang, Liang; Wietgrefe, Stephen W; Fletcher, Courtney V; Lifson, Jeffrey D; Douek, Daniel C; McCune, Joseph M; Haase, Ashley T; Schacker, Timothy W.
Affiliation
  • Estes JD; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Kityo C; Joint Clinical Research Center, Kampala, Uganda.
  • Ssali F; Joint Clinical Research Center, Kampala, Uganda.
  • Swainson L; Division of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Makamdop KN; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, USA.
  • Del Prete GQ; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Deeks SG; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Luciw PA; Department of Pathology and Laboratory Medicine, University of California, Sacramento, Sacramento, California, USA.
  • Chipman JG; Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
  • Beilman GJ; Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
  • Hoskuldsson T; Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
  • Khoruts A; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Anderson J; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Deleage C; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Jasurda J; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Schmidt TE; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Hafertepe M; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Callisto SP; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Pearson H; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Reimann T; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Schuster J; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Schoephoerster J; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Southern P; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Perkey K; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Shang L; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Wietgrefe SW; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Fletcher CV; College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.
  • Lifson JD; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Douek DC; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, USA.
  • McCune JM; Division of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Haase AT; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Schacker TW; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Nat Med ; 23(11): 1271-1276, 2017 Nov.
Article in En | MEDLINE | ID: mdl-28967921
ABSTRACT
In the quest for a functional cure or the eradication of HIV infection, it is necessary to know the sizes of the reservoirs from which infection rebounds after treatment interruption. Thus, we quantified SIV and HIV tissue burdens in tissues of infected nonhuman primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs contained >98% of the SIV RNA+ and DNA+ cells. With ART, the numbers of virus (v) RNA+ cells substantially decreased but remained detectable, and their persistence was associated with relatively lower drug concentrations in LT than in peripheral blood. Prolonged ART also decreased the levels of SIV- and HIV-DNA+ cells, but the estimated size of the residual tissue burden of 108 vDNA+ cells potentially containing replication-competent proviruses, along with evidence of continuing virus production in LT despite ART, indicated two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore challenges in developing 'HIV cure' strategies targeting multiple sources of virus production.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV / Anti-HIV Agents / Viral Load Limits: Humans Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2017 Document type: Article Affiliation country: Estados Unidos
Fulltext
Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV / Anti-HIV Agents / Viral Load Limits: Humans Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2017 Document type: Article Affiliation country: Estados Unidos