2014 “Towards an HIV Cure” symposium Melbourne An Overview of HIV Cure Research in 2014 Diana Finzi, Ph.D. Director, Basic Science Program Division of AIDS, NIH

THE 100 Million “Today I’m pleased to announce a new initiative at the National Institutes of Health to advance research into an HIV cure. We’re going to redirect $100 million into this project to develop a new generation of therapies. Because the United States should be at the forefront of new discoveries into how to put HIV into long-term remission without requiring lifelong therapies -- or, better yet, eliminate it completely.” President Obama World AIDS Day Dec 3, 2013

Why so much talk about “CURE” now?

Walker, range of early treated patients “time to rebound” Chun patient Boston patients Rebound Following Discontinuation of Therapy (modified from Davey)

Residual Virus Latently-infected cells cells? Other cellular compartments? Protected anatomical sites such as gut, brain, lymph nodes?

Homeostasis of Naïve and Memory CD4 T Cells

Establishment and Maintenance of a Latent Reservoir

Long-Lived Resting Memory CD4+T Cells Uninfected Resting Memory CD4+T cell Infected Resting Memory CD4+T cell Relative frequency1,000,0001 Molecules HIV protein00 Molecules HIV RNA00 Base pairs DNA6 x x 10 9 Survival of cell (and progeny)decades

NIH Plans for the Future Basic Research Translational Research Pilot Clinical Studies Phase I-IV Clinical Trials

Cure Web Page

We face complex and difficult challenges We are learning (even from our disappointments) We (the NIH) are working very hard to push for a deeper understanding of what contributes to persistence and to find new strategies to eliminate all forms of HIV in infected people. We face complex and difficult challenges We are learning (even from our disappointments) We (the NIH) are working very hard to push for a deeper understanding of what contributes to persistence and to find new strategies to eliminate all forms of HIV in infected people. Summary