Perspectives for immunotherapy: which applications might achieve an HIV functional cure?

// Vincent Vieillard 1 , Shahin Gharakhanian 2 , Olivier Lucar 1,3 , Christine Katlama 4 , Odile Launay 5 , Brigitte Autran 1,6 , Raphael Ho Tsong Fang 3 , Joël Crouzet 3 , Robert L. Murphy 7 and Patrice Debré 1,6 1 Sorbonne Universités, UPMC Université Paris 06, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France 2 InnaVirVax, Cambridge Innovation Center, Cambridge, MA, USA 3 InnaVirVax, Génopole, Evry, France 4 AP-HP, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, Paris, France 5 Université Paris Descartes, INSERM, CIC 1417, AP-HP, Hôpital Cochin, Paris, France 6 AP-HP, Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, France 7 Center for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Correspondence to: Vincent Vieillard, email: // Keywords : HIV, immunotherapy, functional cure Received : December 14, 2015 Accepted : February 21, 2016 Published : February 29, 2016 Abstract The major advances achieved in devising successful combined antiretroviral therapy (cART) have enabled the sustained control of HIV replication. However, this is associated with costly lifelong treatment, partial immune restoration, chronic inflammation and persistent viral reservoirs. In this context, new therapeutic strategies deserve investigation as adjuncts to cART so as to potentiate immune responses that are capable of completely containing HIV pathogenicity, particularly if cART is discontinued. This may seem a dauntingly high hurdle given the results to date. This review outlines the key research efforts that have recently resurrected immunotherapeutic options, and some of the approaches tested to date. These areas include promising cytokines or vaccine strategies, using different viral or non-viral vectors based on polyvalent “mosaic” antigens and highly conserved HIV envelope peptides, broadly neutralizing antibodies or new properties of antibodies to improve the control of immune system homeostasis. These novel immunotherapeutic strategies appear promising per se , or in combination with TLR-agonists in order to bypass the complexity of the interplay between immune activation, massive CD4 + T-cell loss and viral persistence.