Virological and Immunological Outcomes of Combined Therapeutic Interventions and Dendritic Cell Therapy in People Living with HIV.
Academic Article
Overview
abstract
BACKGROUND: Several strategies have been devised to decrease the size of the HIV reservoir. Except for hematopoietic cell transplantation, therapeutic-driven HIV-1 curative approaches have had limited success. Here we describe a two-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 immune function in people living with HIV in the chronic disease stage of disease and presenting with high CD4 T cell nadirs. METHODS: Thirty participants were enrolled and randomized equally into six 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 (ATI) post intervention, all eligible participants rebounded within 14 weeks, except for one participant with rebound detected at 84 weeks, and two participants receiving all combined therapies who both maintained viral loads below 1000 copies/mL through the study period. These three post-treatment controllers incidentally were all on nicotinamide containing regimens and exhibited immune cellular epigenetic age reversal over the period of the interventions. CONCLUSIONS: This proof-of-concept clinical trial demonstrates the safety of multiple interventions with distinct anti-reservoir activities in people with HIV and argues for continued investigation and investment towards both single and combinatorial intervention towards post-therapy HIV control.
