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Interactive Workshop “HIV Cure 101”: Strategies for Targeting and

Interactive Workshop “HIV Cure 101”: Strategies for Targeting and Eradicating the HIV R eservoir J. D. Lifson AIDS and Cancer Virus Program Leidos Biomedical Research, Inc. Frederick National Laboratory Frederick, MD, United States. http://www.nytimes.com/2011/11/29/health /

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Interactive Workshop “HIV Cure 101”: Strategies for Targeting and

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  1. Interactive Workshop “HIV Cure 101”: Strategies for Targeting and Eradicating the HIV Reservoir J. D. Lifson AIDS and Cancer Virus Program Leidos Biomedical Research, Inc. Frederick National Laboratory Frederick, MD, United States

  2. http://www.nytimes.com/2011/11/29/health/ new-hope-of-a-cure-for-hiv.html?pagewanted=all&_r=0 http://www.advocate.com/news/2009/01/24/aids-hero-martin-delaney-dies-california

  3. Definitions Reservoir: Virus that persists despite apparently effective suppressive cART, and is capable of giving rise to recrudescent infection if/when cART is stopped Cure (definitive treatment beyond lifetime cART): Eradication: Elimination through treatment of all virus capable of giving rise to recrudescent infection if/when cART is stopped Functional Cure (sustained off treatment remission): Not complete elimination of reservoir, but reduction of reservoir to levels sufficiently low, with sufficient host control, to limit/abrogate pathogenesis and minimize/eliminate risk of transmission

  4. Strategy for Development of ART: Understand and Target Vulnerable Steps in Viral Replication Cycle

  5. Parallel Approach for “HIV Cure” • Understand underlying biology of reservoir • Identify potential vulnerable opportunities for intervention (individual, combination) • In vitro, ex vivo, and animal model proof of concept studies with prototype interventions • Clinical evaluation as warranted • Risk/benefit considerations

  6. Challenges for HIV Cure • Reservoirs: Sources of persistent residual virus on suppressive cART that can give rise to recrudescent infection and progressive disease when cART is stopped • Residual virus replication (“active reservoir”) • Long lived infected cells • Latent reservoirs • Epigenetic and transcriptional mechanisms of latency • Anatomic and cell lineage compartments • Pharmacological or immunological sanctuary sites • Must eliminate or control “last virus” capable of recrudescence

  7. Approaches to HIV Cure: Mechanism Based and Empirical • cART intensification • Transcriptional activators • Epigenetic modulators • Immune modulators • Cytokines • Immune checkpoints • Immune targeting (require viral expression) • mAbs • Adoptive cell therapy (engineered cells) • Therapeutic vaccination • Combinations

  8. CMV-vectored vaccines; highly unusual vaccine induced T cell responses • Viral control after i.r, i.vag., and i.v. challenge • Control established over disseminated infection, not just at portal of entry • Progressive clearance of virus over time, including from tissue sites • “Functional cure” and apparent eradication in protected animals

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