Washington D.C., USA, 22-27 July 2012www.aids2012.org
Track A – BASIC SCIENCE
Rapporteur Session
Jacques FellayEPFL, Lausanne, Switzerland
Washington D.C., USA, 22-27 July 2012www.aids2012.org
The A Team
Galit AlterIrene Onyango
Morgane Rolland
Jason Brenchley
Hendrik Streeck
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Viral Eradication: The Cure Agenda
AIDS Research Institute (IrsiCaixa)Autonomous University of Barcelona (UAB)
Catalan Institution for Research and Advanced Studies (ICREA)
Javier Martinez-Picado
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Strategies to cure HIV
Treatmentoptimization& intensification
(eliminateall replication)
Reversal of HIV latency
(increase viral production)
Immune-basedtherapies
(reverse pro-latency signaling)
Therapeuticvaccination
(to enhance host-control)
Genetherapy
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Strategies for depleting the latent HIV reservoir
• Nanoparticle targeting of CD4+ T cells (Jerome Zack)
• Allogeneic bone marrow transplantation (Timothy Henrich)
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Nanoparticles and new PKC activators (Jerome Zack)
• Targeting lipid nanoparticles to CD4 T cells• Loading them with activators of latent virus
expression + anti-HIV drug to inhibit viral spread
Reactivates latently infected cells, minimizes bystander activation and renders new virus non-infectious
Washington D.C., USA, 22-27 July 2012www.aids2012.org
The Structure of Rat Liver Vault at 3.5 Angstrom Resolution Tanaka et al. Science 323, 384 (2009)
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Long-Term Reduction in Peripheral Blood HIV-1 Reservoirs Following Reduced-Intensity
Allogeneic Stem Cell Transplantation in Two HIV-Infected Individuals
Timothy J. Henrich1,2, Gaia Sciaranghella3, Jonathan Z. Li1,2, Sebastien Gallien4, Vincent Ho5,2, Ann S. LaCasce5,2, and Daniel R. Kuritzkes1,2
1Brigham and Women's Hospital, Boston, MA; 2Harvard Medical School, Boston, MA; 3Ragon Institute of MGH, MIT, and Harvard, Boston, MA; 4 Hopital Saint-Louis, Paris, France;
5Dana-Farber Cancer Institute, Boston, MA.
Your logo
Washington D.C., USA, 22-27 July 2012www.aids2012.org
0 100 200 300 400 500 600 700 800 900 1000 1100 1200 13000
50100150200250300
HIV-
1DN
A(c
opie
s/106
PBM
C)
0 100 200 300 400 500 600 700 800 900 1000 1100 1200 13000
200400600800
1000
Days afterHSCT
CD4+
TCe
lls(p
erm
m3))
100% donor lymphochyte
chimerism
<1.8
TND
65 TND
TND
104
VL (clinical lab)
VL (SCA)
<0.5<1.8
<1.8
Patient A
Viral outgrowth assay negative day +1266
No 2-LTRsdetected
Washington D.C., USA, 22-27 July 2012www.aids2012.org
• Allogeneic HSCT with suppressive ART led to a sustained reduction in the HIV-1 reservoir in PBMCs
• What is now required to fully assess the extent of HIV-1 reservoir reduction? Tissue sampling Analytic treatment interruption
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology
Inflammation↑ Endothelium adhesion↑ Monocyte activation
DyslipidemiaHypercoagulation/thrombotic events
Endothelial dysfunction
Microbial translocation
HIV-associated fatMetabolic syndrome
HIV productionHIV replication
CMVExcess pathogens
HIV-mediated loss of regulatory cells (Tregs) Steve Deeks
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Lymph Node Fibrosis (Timothy Schacker)
• Inflammation loss of FRC network in T cell zone of lymph nodes decrease in IL-7 production CD4 T cell apoptosis collagen deposition
Zeng et al., PLoS Pathog. 2012
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Lymph node fibrosis is similar in HIV- individuals in Uganda and in chronic HIV+ individuals in the US
may account for lower baseline CD4+ T cells and less immune reconstitution with ART
may modify the size of the reservoirmay have implications for eradication and cure
in the developing world
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology
Washington D.C., USA, 22-27 July 2012www.aids2012.org
The future of genomics in HIV medicine
• Francis Collins – an NIH perspective• Philip Tarr – a clinician’s perspective
Genomics has the potential to benefit researchers, clinicians and patients
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Third generation long-read sequencing of HIV-1 transcripts discloses cell type specific
and temporal regulation of RNA splicing
Frederic Bushman
International AIDS MeetingWashington DC, 2012
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Combination of two technological advances to explore HIV transcripts at an unprecedented scale:
– Single molecule microdroplet-based digital PCR technology (RainDance)
– High-throughput single molecule real-time sequencing technology (Pacific Bioscience)
Complete message population of HIV-189.6 in CD4+ T cells
• 77 complete message structures
• Evidence for 36 additional transcripts from partial reads
• Total: 113 mRNAs
• 19 novel transcripts including a new completely spliced class (~1kb)
Scott Sherrill-Mix
Washington D.C., USA, 22-27 July 2012www.aids2012.org
A web site for exploring HIV Systems Biology datahttp://microb32.med.upenn.edu/
Be a systems biologist!
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Track A CommitteeDanny Douek Amalio Telenti
Galit AlterFrederic BushmanNicolas Chomont
Genoveffa FranchiniDavid HaerryEsper Kallas
Yves LevySharon Lewin
Thumbi Ndung’uRobert Oelrichs
Javier Martinez-Picado
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Science