SPECIAL COMMENTARIES: Edited by Steven G. DeeksChimeric antigen receptor T-cell therapy for HIV cureAlfageme-Abello, Oscar; Porret, Raphaël; Perreau, Matthieu; Perez, Laurent; Muller, Yannick D.Author Information Lausanne University Hospital (CHUV), Department of Medicine, Division of Immunology and Allergy, Lausanne, Switzerland Correspondence to Yannick D. Muller, MD, PhD, Médecin associé Service d’immunologie et d’allergie Département de médecine (DM) BH010-511 Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. E-mail: [email protected] Current Opinion in HIV and AIDS: March 2021 - Volume 16 - Issue 2 - p 88-97 doi: 10.1097/COH.0000000000000665 Buy Metrics Abstract Purpose of review Cell-based immunotherapies have made enormous progress over the last decade with the approval of several anti-CD19-chimeric antigen receptor (CAR)-T cell therapies for haemato-oncological diseases. CARs are synthetic receptors comprising an antigen-specific extracellular domain fused to a hinge, transmembrane and intracellular signalling domains. The success obtained with CD19 CAR-T cells rekindled interest in using CAR-T cells to treat HIV seropositive patients. The purpose of this review is to discuss historical and recent developments of anti-HIV CARs. Recent findings Since the first description of CD4+-based CARs in the early 90s, new generations of anti-HIV CARs were developed. They target the hetero-trimeric glycoprotein gp120/gp41 and consist of either a CD4+ extracellular domain or a VH/VL segment derived from broadly neutralizing antibodies. Recent efforts were employed in multiplexing CAR specificities, intracellular signalling domains and T cells resistance to HIV. Summary Several new-anti HIV CAR-T cells were successfully tested in preclinical mice models and are now waiting to be evaluated in clinical trials. One of the key parameters to successfully using CAR-T cells in HIV treatment will depend on their capacity to control the HIV reservoir without causing off-targeting activities. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.