Immunorecovered but Exhausted: Persistent PD-1/PD-L1 Expression Despite Virologic Suppression and CD4 Recovery in...

Area of Science:

• Immunology
• Virology
• Public Health

Background:

• Antiretroviral therapy (ART) effectively suppresses HIV viremia but often fails to fully restore immune function in people with HIV (PLWH).
• Persistent immune dysfunction and exhaustion are observed in some PLWH despite virologic control.
• Understanding immune recovery and exhaustion markers is crucial for optimizing HIV management.

Purpose of the Study:

• To compare immune recovery and exhaustion markers (PD-1/PD-L1 expression) between newly diagnosed and long-term ART-treated individuals with HIV.
• To assess the utility of traditional immune parameters (CD4+ count, CD4+/CD8+ ratio) versus exhaustion markers in evaluating immune status.

Main Methods:

• Analysis of 79 PLWH, including 52 newly diagnosed (12-month follow-up) and 27 long-term treated (Ukrainian refugees).
• Flow cytometry to measure CD4+ and CD8+ counts, CD4+/CD8+ ratio, and PD-1/PD-L1 expression on lymphocytes (CD3+, CD4+, CD19+).
• Linear regression models incorporating ART regimen and HIV subtype as covariates.

Main Results:

• Newly diagnosed individuals had higher CD8+ counts (p=0.028) and a lower CD4+/CD8+ ratio (p=0.0027) at 12 months compared to long-term treated.
• Significantly elevated immune exhaustion markers (CD4+ PD-1+, CD3+ PD-1+) were found in newly diagnosed individuals (p<0.0001).
• Group membership independently predicted higher percentages of CD3+, CD4+, and CD19+ cells (p<0.001).

Conclusions:

• Despite virologic suppression and CD4+ count recovery, newly diagnosed PLWH exhibit elevated immune exhaustion markers, suggesting incomplete immune normalization.
• Standard immune parameters like CD4+ count and CD4+/CD8+ ratio may not fully reflect immune status in PLWH.
• Broader immunologic profiling, including exhaustion markers, is warranted for comprehensive HIV care.