- •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.
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.
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.
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.
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.
Abbreviations: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)
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Accepted: March 9, 2023
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