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The Future of HIV/AIDS: The Road to a Cure How HIV persists during therapy? Viral replication T cell survival Proliferation Courtesy of Nicholas Chomont 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) 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” Cytokines, chemical compounds… Uninfected cells HIV-induced cell death 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 Courtesy of Nicholas Chomont Antibodies, cytokines, gene therapy, chemotherapy Proliferation While we are searching: Keep patients ready by: Universal Access Inspired from Sharon Lewin 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 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