As we enter the fourth decade in HIV epidemic, advances in understanding HIV pathogenesis and development of potent and safer antiretroviral drugs have been spectacular. More than 30 antiviral drugs have been registered and the impact of combination antiviral therapy on morbidity and mortality has been dramatic. However, despite long-term virus suppression, HIV invariably rebounds after interruption of therapy. Long-term antiviral therapy does not cure HIV infection nor does it induce restoration/development of virus-specific immune responses capable of controlling HIV replication. Therefore, development of immune-based interventions is needed to restore effective defenses that can lead to HIV functional cure and ultimately eradication.
Therapeutic vaccination and immune interventions that generate de-novo or that boost preexisting HIV-specific T-cell responses are being investigated as a potential means to achieve a ‘functional HIV cure’. One major hurdle in the quest of an HIV cure is control and elimination of the HIV latent reservoir. Several immune interventions that target the latent reservoir have been tried in recent years. In parallel, several therapeutic vaccination strategies have been developed and tested in early clinical studies. Recent encouraging studies show for the first time that vaccination can have an impact on HIV load.
This review summarizes the main immune interventions evaluated over the last years. Ways to improve them, as well as challenges in monitoring/evaluating effects of such strategies, are being discussed. In addition, clinical efficacy and potential clinical benefits of immunotherapeutic interventions are particularly difficult to measure. This review highlights current assays used and their shortcoming.
aDivision of Immunology and Allergy and Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
bINSERM U955, Université Paris Est Créteil, Faculté de Médecine, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Vaccine Research Institute, Creteil, France
Correspondence to Giuseppe Pantaleo, Centre Hospitalier Universitaire Vaudois (CHUV), Department of Medicine, Division of Immunology and Allergy (IAL), Bugnon 46 - BH10-527, 1011 Lausanne, Switzerland. Tel: +41 0 21 314 10 63; fax: +41 0 21 314 10 70; e-mail: firstname.lastname@example.org