Antibody-mediated prevention and treatment of HIV-1 infection

Abstract

Novel broadly neutralizing antibodies targeting HIV-1 hold promise for their use in the prevention and treatment of HIV-1 infection. Pre-clinical results have encouraged the evaluation of these antibodies in healthy and HIV-1-infected humans. In first clinical trials, highly potent broadly neutralizing antibodies have demonstrated their safety and significant antiviral activity by reducing viremia and delaying the time to viral rebound in individuals interrupting antiretroviral therapy. While emerging antibody-resistant viral variants have indicated limitations of antibody monotherapy, strategies to enhance the efficacy of broadly neutralizing antibodies in humans are under investigation. These include the use of antibody combinations to prevent viral escape, antibody modifications to increase the half-life and the co-administration of latency-reversing agents to target the cellular reservoir of HIV-1. We provide an overview of the results of pre-clinical and clinical studies of broadly HIV-1 neutralizing antibodies, discuss their implications and highlight approaches for the ongoing advancement into humans.

Keywords: (S)HIV animal models; Clinical trials; Fc-mediated activity; HIV-1 broadly neutralizing antibodies; Immunotherapy; Neutralization; Passive immunization.

Fig. 1

Clinical trials of new-generation broadly neutralizing antibodies. Numbers show (prospective) trial participants receiving bNAb(s). Letters encode the ClinicalTrials.gov study identifier. Healthy and HIV-1-infected individuals are indicated by green and red colors, respectively. Studies shown in dark colors have been completed, while studies shown in light colors are ongoing or not yet recruiting. Asterisk indicates that the number of participants includes those receiving placebo