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

Abstract

Abstract Background Despite significant progress made in healthcare for PLWHA, many patients still present or re-visit healthcare centers, with advanced HIV disease, increasing their risk of death. The main causes of advanced disease are late initiation of treatment and low adherence to ART. Soluble immunological markers have prognostic significance in clinical medicine, but it is not clear whether irregular use of ART influences levels of circulating cytokines. Therefore, this study aimed to evaluate the association of cytokines to predict mortality among hospitalized PLWHA. In addition, the study evaluated the greater risk of death between ART-naive and ART-non-adherent HIV + patients with advanced disease and quantified the levels of immunological markers in postmortem whole blood samples to assess if they can be influenced by irregular use of ART. Methods Longitudinal observational study was carried out at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus, Brazil. In total, 111 participants were conveniently recruited between 2019 to 2021. Clinical and laboratory data were obtained from electronic medical records. From patient plasma samples, 27 types of cytokines/chemokines were measured using the Luminex Multiplex Assay within 72 hours of patient admission and 6 hours after death. Results Respiratory syndromes being the main causes of hospitalization. Pulmonary tuberculosis, neurotoxoplasmosis and oropharyngeal-esophageal candidiasis were the most prevalent opportunistic infections. The risk of death is higher among ART-naïve PLWHA. The levels of most of the 27 immunological markers were higher in those who died and post-mortem than those who were discharged from hospitalization. The increased levels of IFNγ, CCL2 and CCL3 were associated with death and increased levels of immunological markers in ART-naïve PLWH were associated with CD4 cell counts. The multivariate model showed that among post-mortem immunological markers, increased IL-17 was associated with ART-naïve PLWHA, while increased IFNγ was associated with ART experienced individuals. Conclusions ART-naïve PLWHA hospitalized with advanced disease have a higher risk of death. Some immunological markers are possible predictors of death upon hospital admission due to HIV/AIDS, and their levels increased at post-mortem. Our findings suggest a polarized response to IL-17 and IFNγ among ART-naïve and ART-experienced PLWHA, respectively.