Rapporteur Session
Jacques Fellay
EPFL, Lausanne, Switzerland www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Jason Brenchley
The A Team
Galit Alter
Irene Onyango
Morgane Rolland Hendrik Streeck www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Viral Eradication: The Cure Agenda
Javier Martinez-Picado
AIDS Research Institute (IrsiCaixa)
Autonomous University of Barcelona (UAB)
Catalan Institution for Research and Advanced Studies (ICREA) www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Strategies to cure HIV
Gene therapy
Treatment optimization
& intensification
(eliminate all replication)
Therapeutic vaccination
Reversal of
HIV latency
(to enhance host-control)
(increase viral production)
Immune-based therapies
(reverse pro-latency signaling) www.aids2012.org
Washington D.C., USA, 22-27 July 2012

• Nanoparticle targeting of CD4+ T cells
(Jerome Zack)
• Allogeneic bone marrow transplantation
(Timothy Henrich) www.aids2012.org
Washington D.C., USA, 22-27 July 2012

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 www.aids2012.org
Washington D.C., USA, 22-27 July 2012

The Structure of Rat Liver Vault at 3.5 Angstrom Resolution
Tanaka et al. Science 323, 384 (2009) www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Your logo
Long-Term Reduction in Peripheral Blood HIV-1
Reservoirs Following Reduced-Intensity
Allogeneic Stem Cell Transplantation in Two HIV-
Infected Individuals
Timothy J. Henrich 1,2 , Gaia Sciaranghella 3 , Jonathan Z. Li 1,2 , Sebastien Gallien 4 ,
Vincent Ho 5,2 , Ann S. LaCasce 5,2 , and Daniel R. Kuritzkes 1,2
1 Brigham and Women's Hospital, Boston, MA; 2 Harvard Medical School, Boston, MA; 3 Ragon Institute of MGH, MIT, and Harvard, Boston, MA; 4 Hopital Saint-Louis, Paris, France;
5 Dana-Farber Cancer Institute, Boston, MA.
www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Patient A
No 2-LTRs detected
VL
(clinical lab)
VL
(SCA)
TN
D
104
<1
.8
<1
.8
65
<1
.8
<1
.8
TN
D
TN
D
<0
.5
300
250
200
150
100
50
0
100% donor lymphochyte chimerism
Viral outgrowth assay negative day +1266
0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300
1000
800
600
400
200
0
0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300
Days after HSCT www.aids2012.org
Washington D.C., USA, 22-27 July 2012

• 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 www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology www.aids2012.org
Washington D.C., USA, 22-27 July 2012

HIV production
HIV replication
HIV-associated fat
Metabolic syndrome
CMV
Excess pathogens
Inflammation
↑ Endothelium adhesion
↑ Monocyte activation
Dyslipidemia
Hypercoagulation/ thrombotic events
Endothelial dysfunction
HIV-mediated loss of regulatory cells (Tregs) Steve Deeks
Microbial translocation

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 www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Lymph node fibrosis is similar in HIVindividuals 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 reservoir
 may have implications for eradication and cure in the developing world www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Hot Topics
1. Reservoirs & latency
2. Inflammation & fibrosis
3. Genomics & systems biology www.aids2012.org
Washington D.C., USA, 22-27 July 2012

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 www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Third generation long-read sequencing of HIV-1 transcripts discloses cell type specific and temporal regulation of
RNA splicing
Frederic Bushman
International AIDS Meeting
Washington DC, 2012 www.aids2012.org
Washington D.C., USA, 22-27 July 2012

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) www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Complete message population of HIV-1
89.6
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

A web site for exploring HIV Systems Biology data http://microb32.med.upenn.edu/
Be a systems biologist!
www.aids2012.org
Washington D.C., USA, 22-27 July 2012

Track A Committee
Danny Douek Amalio Telenti
Galit Alter
Frederic Bushman
Nicolas Chomont
Genoveffa Franchini
David Haerry
Esper Kallas www.aids2012.org
Yves Levy
Sharon Lewin
Thumbi Ndung’u
Robert Oelrichs
Javier Martinez-Picado
Washington D.C., USA, 22-27 July 2012

www.aids2012.org
Washington D.C., USA, 22-27 July 2012