Viral coinfections and checkpoint-marker expression in HIV: An exploratory HCV-Related CD4⁺ T-Cell PD-L1 pattern

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Chronic viral coinfections are implicated in immune dysregulation among people with HIV.
• The relationship between coinfections like Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Cytomegalovirus (CMV) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in HIV is not well understood.

Purpose of the Study:

• To investigate the association between chronic viral coinfections (HBV, HCV, CMV) and PD-1/PD-L1 expression in people with HIV.
• To analyze changes in PD-1 and PD-L1 expression on CD4+ T cells and CD19+ B cells over 12 months in relation to viral coinfection status.

Main Methods:

• Analysis of 100 people with HIV with suppressed viral load (<50 copies/mL) at 12-month follow-up.
• Evaluation of baseline HBV contact, HCV status (RNA positive/negative), and CMV IgG serostatus.
• Measurement of PD-1 and PD-L1 expression on CD4+ T cells and CD19+ B cells, including composite indices.

Main Results:

• No significant association was found between HBV contact or CMV IgG serostatus and PD-1/PD-L1 expression.
• Longitudinal changes in CD4+ T-cell PD-L1 expression across HCV groups were not statistically significant after correction for multiple comparisons.
• An exploratory analysis suggested a potential increase in CD4+ T-cell PD-L1 in participants with positive HCV RNA at baseline.

Conclusions:

• HBV and CMV coinfections do not appear to be consistently associated with PD-1/PD-L1 expression in people with HIV.
• The observed trend linking HCV RNA positivity to increased CD4+ T-cell PD-L1 is hypothesis-generating and requires prospective validation.