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