Inflammation burden score in multidrug-resistant HIV-1 infection. Issue 5 (May 2023)

• Record Type: Journal Article
• Authors: Clemente, Tommaso; Caccia, Roberta; Galli, Laura; Galli, Andrea; Poli, Andrea; Marchetti, Giulia Carla; Bandera, Alessandra; Zazzi, Maurizio; Santoro, Maria Mercedes; Cinque, Paola; Castagna, Antonella; Spagnuolo, Vincenzo
• Is Part Of: Journal of infection. Volume 86:Issue 5(2023)
• Page Start: 453
• Page End: 461
• Publication Date: 2023-05
• Subjects: AIDS acquire immunodeficiency syndrome -- ART antiretroviral therapy -- BDG (1, 3)-β-D-glucan -- CRP C-reactive protein -- CTLA4 cytotoxic T-lymphocyte-associated protein 4 -- DMEM Dulbecco's Modified Eagle Medium -- EndoCAb endotoxin core immunoglobulin G -- FBS fetal bovine serum -- HAVCR2 or Tim-3 hepatitis A virus cellular receptor 2 -- HBsAg hepatitis B surface antigen -- HCV hepatitis C virus -- HIV human immunodeficiency virus -- HLA human leukocyte antigen -- hs high sensitivity -- IBS inflammation burden score -- IL interleukin -- INSTI integrase strand transfer inhibitor -- IQR interquartile range -- MACE major adverse cardiovascular event -- MDR multidrug-resistant -- NRTI nucleoside reverse transcriptase inhibitor -- NNRTI non-nucleoside reverse transcriptase inhibitors -- PBMC peripheral blood mononuclear cell -- PDCD1 or PD-1 programmed cell death protein 1 -- PI protease inhibitor -- PLWH people living with HIV -- PYFU person-years of follow-up -- s soluble -- TNF tumor necrosis factor -- 4DR four-class drug-resistant -- 95%CI 95% confidence interval; HIV -- Drug resistance -- Inflammation -- Immune activation -- Bacterial translocation -- Immunosenescence; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2023.03.011
• Languages: English
• ISSNs: 0163-4453

Abstract

Summary: Objectives: Four-class drug-resistant (4DR) people living with HIV (PLWH) are a fragile population with a high burden of disease. No data on their inflammation and T-cell exhaustion markers are currently available. Methods: Inflammation, immune activation and microbial translocation biomarkers were measured through ELISA in 30 4DR-PLWH with HIV-1 RNA ≥ 50 copies/mL, 30 non-viremic 4DR-PLWH and 20 non-viremic non-4DR-PLWH. Groups were matched by age, gender and smoking habit. T-cell activation and exhaustion markers were assessed by flow cytometry in 4DR-PLWH. An inflammation burden score (IBS) was calculated from soluble marker levels and associated factors were estimated through multivariate regression. Results: The highest plasma biomarker concentrations were observed in viremic 4DR-PLWH, the lowest ones in non-4DR-PLWH. Endotoxin core immunoglobulin G showed an opposite trend. Among 4DR-PLWH, CD38/HLA-DR and PD-1 were more expressed on CD4 + (p = 0.019 and 0.034, respectively) and CD8 + (p = 0.002 and 0.032, respectively) cells of viremic compared to non-viremic subjects. An increased IBS was significantly associated with 4DR condition, higher values of viral load and a previous cancer diagnosis. Conclusions: Multidrug-resistant HIV infection is associated with a higher IBS, even when viremia is undetectable. Therapeutic approaches aimed to reduce inflammation and T-cell exhaustion in 4DR-PLWH need to be investigated. Highlights: Matched-cohort study on four-class drug-resistant (4DR) and non-4DR-PLWH. Inflammation burden score (IBS) was calculated from plasma levels of 9 biomarkers. IBS was higher in 4DR-PLWH, even when non-viremic, than in non-4DR-PLWH. T cells were more 'exhausted' in viremic than non-viremic 4DR-PLWH. Further studies on treatments targeting these pathways in 4DR-PLWH are required.