The Future of HIV/AIDS: The Road to a Cure

How HIV persists during therapy?  Ongoing viral replication occurs in subjects on suppressive HAART (TW Chun, JCI; N Tobin, J Virol 2005).  HIV integrate in long lived resting memory T cells and persist despite suppressive HAART (TW Chun, Nat. Med 1995, D Finzi, Science ; TW Chun, PNAS 1997).  Reservoir cells, like other memory T cells, divide very slowly to maintain the memory of the immune system (A. Bosque and V. Planelles) T cell survival Proliferation Viral replication Courtesy of Nicholas Chomont

What is our goal? Eradication vs Remission

What strategies to control/eradicate reservoirs? 1/2  Intensification of HAART (+/- other interventions)  Early initiation of HAART (limit viral reservoirs)  Improved Drugs (penetrating anatomical compartments)  Reactivation of HIV replication from latent reservoirs:  ”Shock and Kill” HIV-induced cell death Uninfected cells Cytokines, chemical compounds… Courtesy of Nicholas Chomont

What strategies to control/eradicate reservoirs? 2/2  Interfering with immunological mechanism that contribute to HIV persistence  Other therapeutic interventions (Gene/Mol therapy, therapeutic vaccine) T cell survival Proliferation Antibodies, cytokines, gene therapy, chemotherapy Courtesy of Nicholas Chomont

While we are searching:  Keep patients ready by:  Universal Access  Early Treatment - Limit reservoirs and preserve the immune system  Invest in research:  Better understanding of biological mechanism and role of the immune system in establishing reservoirs and persistence  Better tools and models  In vitro and in vivo models  More precise assays and sensitive techniques  Drug development: increased specificity for latently infected cells  Develop translational research Inspired from Sharon Lewin

Global Scientific Strategy Towards an HIV Cure While the Global Fund keeps working towards Universal Access:  IAS to coordinate and support the creation of an international multidisciplinary scientific advisory group on HIV Reservoirs to develop a Global Scientific Strategy « Towards an HIV Cure »  A Global Scientific Consortium « Towards an (functional) HIV Cure » ?

Acknowledgements International AIDS Society, Geneva: Shirin Heidari Marie-Capucine Penicaud Tamara Torri Julie Pluies Anthony Flynn With courtesy of members of IAS Core Group Towards An HIV Cure who shared their slides: Nicolas Chomont, Vaccine and Gene Therapy Institute Florida, USA Tae-Wook Chun, National Institutes of Health, USA Sharon Lewin, Burnet Institute, Melbourne, Australia