Spectral immunophenotyping of innate immune cells from people living with HIV treated with TLR9 agonist and bNAbs

Abstract

With the emergence of Antiretroviral Therapy (ART), there was an improvement in the quality of life and reduction in mortality of people infected with HIV. However, HIV has become a chronic disease since treatment is not able to eliminate the virus, which remains in a latent state in cells and tissues. In this way, ideally, the treatment of people living with HIV should be continuous and uninterrupted from the diagnosis, since the interruption of the administration of antiretroviral drugs leads to the remission of the viral load within a few weeks. However, drugs have long-term cytotoxic effects, and the presence of the virus, even if latent, induces a basal inflammatory state, favoring the onset of diseases such as metabolic syndromes. In this context, new approaches have been sought aimed at reducing viral reservoirs and viremic control without the use of daily medication. As only ART and the action of the immune system are not capable of efficiently eliminating infected cells and preventing the infection of other cells, new strategies have been administered. The shock and kill therapy has as its principle the use of ART together with a latency reversal agent (LRA), aiming at reducing or eliminating the viral reservoir. In this sense, boost the immune system is one of the strategies used and has been tested in the clinical trial NCT03837756 of the Aarhus University. In the clinical study, the TLR9 agonist (MGN1703) and two broadly neutralizing antibodies (bNAbs - 3BNC117 and 10-1074) were used. One of the hypotheses of the study is that the innate immune system may also be modulated after treatment and that these effects may be related to the control of viral load in cellular reservoirs. Therefore, the aim of this work is to evaluate the expression of receptors on the surface of innate immunity cells using the spectral flow cytometry methodology and correlate with the ability to maintain virological control even in the absence of ART. (AU)