Hocqueloux, L. et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS 24, 1598-1601

Service de Maladies Infectieuses et Tropicales, CentreHospitalier Régional d'Orléans -La Source, Orléans Cedex 2, France.
AIDS (London, England) (Impact Factor: 5.55). 06/2010; 24(10):1598-601. DOI: 10.1097/QAD.0b013e32833b61ba
Source: PubMed


Five out of 32 patients who received very early and prolonged antiretroviral therapy displayed an unusual, sustained immunovirological control after treatment discontinuation (mean duration: 77 months). These 'post-treatment controllers' did not have the genetic characteristics of spontaneous 'elite' controllers, although they shared very low and stable level of viral reservoir. Treatment may have dramatically decreased this reservoir and preserved potent HIV-specific immunologic responses, inducing a new balance between the virus and the host's immune system in these patients.

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    • "Interestingly, it has been found that a relatively low viral load environment during primary infection in LTNP/EC may be the crucial difference with progressors [25]. Accordingly, early initiated HAART therapy in HIV patients allows long-term control of infection after the interruption of the treatment [26] [27] [28]. Our focus was on the development of lentiviral-based DNA vaccines that mimic the early stages of lentivirus infection to stimulate natural and proportionate immune responses against virus antigens. "
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    ABSTRACT: Novel HIV vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA vaccine "CAL-SHIV-IN(-)" that undergoes a single round of replication in the absence of integration resulting in augmented expression of vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this vaccine prototype was increased by the removal of the integrase coding sequences from the pol gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN(-) DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the vaccine. A single dose DNA immunization of humanized NOD/SCID/β2 mice showed a substantial increase of IFN-γ-ELISPOT in splenocytes compared to the former replication and integration defective Δ4SHIV-KU2 DNA vaccine. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Mar 2015 · Vaccine
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    • "News such as the case report of the cure of an ostensibly HIV+ baby treated in the very early phase of the disease [30] and, more importantly, the results of the ANRS VISCONTI study [29] have been hailed with widespread enthusiasm. Of particular note, up to ≈ 15% of the early treated individuals have been shown to display spontaneous control of viremia following STI [27]. However, the rate of post-therapy control following ART administration during the acute phase may be lower (≈5%) according to another report [28]. "
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    ABSTRACT: Despite the huge clinical success of antiretroviral therapy, several factors such as side effects, requirement of life-long adherence, high cost, incomplete access to therapies and development of drug resistance make the quest for an ultimate cure of HIV/AIDS a worldwide priority of biomedical research. In this respect, several sterilizing or functional cures have been reported in the last years in both non-human primates and humans. This review provides a summary of the main results achieved so far, outlining their strengths as well as their limitations. A synthetic interpretation of these results could be pivotal in order to develop an effective and widely available cure.
    Full-text · Article · Nov 2013 · Retrovirology
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    • "This change was associated with enhanced specific immune responses following viral rebound after therapy suspension, thus suggesting the establishment of an “immune state” [7]. Similar effects had previously been observed only in the period immediately after acute infection but not in a pre-AIDS stage [21,39-41]. Although fully controlled studies involving larger numbers of macaques will be necessary in order to obtain further mechanistic insight, it is becoming increasingly evident that dramatic changes in disease progression cannot be evaluated only in terms of sheer numbers of study subjects [38,43]. "
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    ABSTRACT: Background HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia. Results We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8+ cells and associated with enhanced levels of cell-mediated immune responses. Conclusions The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current "ART for life" plight.
    Full-text · Article · Jul 2013 · Retrovirology
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