1. Washington D.C., USA, 22-27 July 2012www.aids2012.org Track A – BASIC SCIENCE Rapporteur Session Jacques Fellay EPFL, Lausanne, Switzerland

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

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

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

5. 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

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

7. 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)

8. 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

9. 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)

10. 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. 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. Your logo

11. Washington D.C., USA, 22-27 July 2012www.aids2012.org Patient A Viral outgrowth assay negative day +1266 No 2-LTRs detected

12. 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

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

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

15. 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

16. 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 reservoir  may have implications for eradication and cure in the developing world

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

18. 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

19. 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 Meeting Washington DC, 2012

20. 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)

21. 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

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

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

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