interactive workshop “hiv cure 101”: strategies for targeting and
DESCRIPTION
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 / - PowerPoint PPT PresentationTRANSCRIPT
Interactive Workshop
“HIV Cure 101”:Strategies for Targeting and
Eradicating the HIV Reservoir
J. D. LifsonAIDS and Cancer Virus ProgramLeidos Biomedical Research, Inc.
Frederick National LaboratoryFrederick, MD, United States
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
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
Strategy for Development of ART:Understand and Target Vulnerable Steps in Viral Replication Cycle
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
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
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
• 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