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HIV Cure Discovery: Functional HIV Cure in Rhesus Macaque Monkey Can Be Model for Humans
 
 
  "A small proportion of HIV-infected patients control viral replication and disease progression in the absence of any antiretroviral treatment. Understanding the mechanisms of viral control in these elite controllers may help to identify new therapeutic approaches in order to control HIV infection......We identified an animal model (the rhesus macaque infection with SIVagm) in which, after massive acute viral replication and CD4+ T cell depletion, SIV infection is controlled in 100% of cases during chronic infection........this new model addresses an immediate need in AIDS research: deciphering the mechanisms and biomarkers of durable and effective control of SIV replication.......This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status."
 
"Only a fraction of EC patients (the "super-elites"), achieve control of immune activation close to baseline levels, in addition to the control of viral replication. These patients sustain CD4+ T cell counts and preserved CD8+ T cell function [Landay, unpublished] and are probably the best examples of functional cure of HIV infection. Even if these patients represent a minority of the HIV infected patients, understanding the mechanisms through which the functional cure of HIV infection occurs in the absence of antiretroviral therapy is probably the most important information that can be derived from the study of controlled HIV/SIV infections for both vaccine development and HIV eradication efforts. Our new animal system models these super-elite controllers, which are the most difficult to model in animal systems and therefore it is a major achievement in the field, as it can be used to identify the factors driving the infection to elite controlled status overcoming the most important limitation to the study of the functional cure, which is that control cannot be predicted at the time when the virus actively replicate during the early stages of infection."
 
A New Siman Model Could Help Finding a HIV Functional Cure
 
http://www.hiv-reservoir.net/index.php/Latest-News-on-HIV-Reservoirs-Eradication/a-model-of-super-elite-controllers.html
 
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PLoS Pathogens: Functional Cure of SIVagm Infection in Rhesus ...
 
(2011) Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4+ T Cells and Is Reverted by CD8+ Cell Depletion. PLoS
 
Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4+ T Cells and Is Reverted by CD8+ Cell Depletion
 
Ivona Pandrea1,2,3, Thaidra Gaufin4, Rajeev Gautam4, Jan Kristoff3, Daniel Mandell4, David Montefiori5, Brandon F. Keele6, Ruy M. Ribeiro7, Ronald S. Veazey1, Cristian Apetrei3,4,8*
 
1 Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, United States of America, 2 Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 4 Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, United States of America, 5 Department of Surgery, Duke University, Durham, North Carolina, United States of America, 6 SAIC Frederick, Inc, NCI, NIH, Frederick, Maryland, United States of America, 7 Los Alamos National Laboratory, Los Alamos New Mexico, United States of America, 8 Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
 
Author Summary
 
"A small proportion of HIV-infected patients control viral replication and disease progression in the absence of any antiretroviral treatment. Understanding the mechanisms of viral control in these elite controllers may help to identify new therapeutic approaches in order to control HIV infection. However, elite controllers are identified AFTER control is established, therefore it is difficult to identify the virus and host factors that drive the infection to the controlled status. We identified an animal model (the rhesus macaque infection with SIVagm) in which, after massive acute viral replication and CD4+ T cell depletion, SIV infection is controlled in 100% of cases during chronic infection. This "functional cure" of SIVagm infection in rhesus macaques results in a complete immune restoration after four years and can be reverted by depleting the cellular immune responses in vivo. An animal model of elite controlled lentiviral infection in which complete control can be predicted in all cases permits research on the early events of infection when host factors are actively driving the infection towards the controlled status to understand the pathogenesis of HIV/SIV infections and design of new approaches for controlling HIV infection."
 
"We conclude that SIVagm infected RMs represent a valuable model of super elite controlled infection which can be used to: (i) examine virologic and immunologic changes during early infection that may lead to the infection control; (ii) perform invasive studies facilitating concomitant investigations in a large array of tissues collected at critical time points of infection; (iii) perform in vivo manipulation of SIV pathogenesis by selective depletion of different cellular subsets, or experimental modulation of immune activation to assess their contribution to the control of VL. Such experiments have not been and cannot be pursued in studies of human HIV-1 ECs and thus, this new model addresses an immediate need in AIDS research: deciphering the mechanisms and biomarkers of durable and effective control of SIV replication."
 
"In this study, we showed that rhesus macaque infection with SIVagm results in an infection pattern that models that of elite controlled HIV infection in 100% of cases. Acute SIVagm infection of RMs was similar to pathogenic infection, being characterized by robust acute viral replication and massive mucosal CD4+ T cell depletion. However, during the chronic stage of infection, SIVagm was eventually completely controlled in all RMs in blood and tissues. Inflammation and apoptosis were resolved at mucosal sites, microbial translocation was controlled, immune activation returned to baseline levels and mucosal CD4+ T cells were completely restored in RMs infected with SIVagm. We also report that SIVagm elite controlled infection in RMs could be reverted by experimental depletion of CD8+ cells, suggesting that, similar to HIV-infected human elite controllers, cellular immune responses are involved in the control of SIVagm infection in RMs. Therefore, this new animal model of elite controlled infection may be used to model the viral and host factors involved in the achievement of long-term control of HIV replication in the absence of antiretroviral therapy, i.e., the "functional cure" of HIV infection."
 
 
 
 
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