Virological and Immunological Outcomes of Combined Therapeutic Interventions and Dendritic Cell Therapy in People With HIV.
Academic Article
Overview
abstract
BACKGROUND: Except for hematopoietic cell transplantation, therapeutic-driven HIV-1 curative approaches have been unsuccessful. Here, we describe a 2-step randomized clinical trial designed to evaluate the safety and impact of individual and combinatorial therapeutic strategies on changes in peripheral and gut mucosal HIV reservoirs, immune activation and function in people with HIV with chronic disease and high CD4 T-cell nadirs. METHODS: Thirty participants were enrolled and randomized equally into 6 study arms based on treatments with either standard antiretroviral therapy (ART) alone or a combination of candidate anti-HIV reservoir strategies that included ART intensification, auranofin (an apoptotic-inducer antirheumatic drug), nicotinamide (vitamin B3), and a personalized dendritic cell therapy. RESULTS: After an analytical treatment interruption post intervention, all eligible participants rebounded within 14 weeks, except for 1 participant with rebound detected at 84 weeks and 2 participants receiving all combined therapies maintained viral loads below 1000 copies/mL through the study period. These posttreatment controllers all received nicotinamide containing regimens and exhibited immune cellular epigenetic age reversal. CONCLUSIONS: This proof-of-concept clinical trial demonstrates the safety of multiple interventions with distinct antireservoir activities in people with HIV and argues for continued investigation of both single and combinatorial interventions towards posttherapy HIV control.
