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Updated: Aug 12, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Viral coinfections and checkpoint-marker expression in HIV: An exploratory HCV-Related CD4⁺ T-Cell PD-L1 pattern
Bogusz Aksak-Wąs1, Karolina Skonieczna-Żydecka2, Danuta Cembrowska-Lech3
1Department of Infectious, Tropical Diseases and Acquired Immunodeficiency. Pomeranian Medical University in Szczecin, Szczecin, Poland. bogusz.aksak.was@pum.edu.pl.
Insights
Chronic viral coinfections in people with HIV may impact immune regulation. Hepatitis C virus (HCV) infection showed a potential link to increased PD-L1 expression on CD4+ T cells, warranting further investigation.
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.
Abstract:
Chronic viral coinfections may contribute to persistent immune dysregulation in people with HIV, but their association with PD-1/PD-L1 expression remains uncertain. We analysed 100 people with HIV using available-case endpoint analyses and marker-specific paired baseline-to-follow-up analyses. Follow-up was scheduled at 12 months (allowable window, 9-15 months), and all participants had HIV RNA < 50 copies/mL at the endpoint. Baseline HBV contact, HCV status, and CMV IgG serostatus were evaluated in relation to PD-1 and PD-L1 expression on CD4⁺ T cells and CD19⁺ B cells and exploratory composite checkpoint-expression indices. HBV contact and CMV IgG serostatus were not associated with reproducible differences. The global comparison of longitudinal CD4⁺ T-cell PD-L1 change across HCV groups did not remain significant after false-discovery-rate correction; an exploratory pairwise comparison suggested a greater increase in participants with baseline HCV RNA positivity. Overall, the HCV-related pattern was hypothesis-generating and requires prospective validation.
