Association between cytokine and increased risk of death in ART- naïve and ART-non-adherence patients hospitalized with advanced HIV disease

Abstract

Background

Despite progress in healthcare for people living with HIV/AIDS (PLWHA), many still present with advanced HIV, thus increasing their risk of death. Late initiation of treatment and poor adherence to antiretroviral therapy (ART) are key contributing factors. This study aimed to evaluate cytokines as mortality predictors among hospitalized PLWHA. It assessed the risk of death between ART-naïve and ART-non-adherent PLWHA with advanced HIV and quantified immunological markers in post-mortem samples to determine the influence of irregular ART use.

Methods

A longitudinal observational study was conducted at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus, Brazil, with 111 participants recruited between 2018 and 2019. Clinical and laboratory data were obtained from electronic medical records. Plasma samples were analyzed for 27 cytokines/chemokines using the Luminex^® multiplex assay within 72 h of admission and 6 h after post-mortem.

Results

ART-naïve PLWHA had a higher risk of death. Most of the 27 immunological markers analyzed in the post-mortem were elevated in those who died compared to those who were discharged. Increased levels of IFNγ, CCL2, and CCL3 were associated with death. Elevated immunological markers in ART-naïve PLWHA correlated with CD4 cell counts. Notably, IL-17 increased in ART-naïve PLWHA, while IL-2 increased in ART-non-adherent PLWHA, indicating a dichotomy. T helper-2 responses were marked by IL-9 in ART-naïve and IL-5 in ART-non-adherent PLWHA.

Conclusions

ART-naïve PLWHA hospitalized with advanced HIV have a higher risk of death. Some immunological markers are possible predictors of death upon hospital admission due to HIV/AIDS, and their levels were found to be increased in post-mortem blood samples. Our findings suggest a polarized response among ART-naïve and ART-non-adherent PLWHA.