Persistently Elevated Expression of Systemic, Soluble Co-Inhibitory Immune Checkpoint Molecules in People Living with HIV before and One Year after Antiretroviral Therapy
Abstract
:1. Introduction
2. Methods
3. Results
3.1. CD4+ Cell Counts and Viral Loads
3.2. Comparison of Plasma Concentrations of the Test Soluble Co-Inhibitory Immune Checkpoints between PLWH and Control Participants, as well as before and after ART
3.3. Impact of Disease Severity on the Plasma Concentrations of the Soluble Co-Inhibitory Immune Checkpoints
3.4. Effects of Tobacco Usage on the Plasma Concentrations of the Soluble Co-Inhibitory Immune Checkpoints in PLWH before and after ART
3.5. Correlations between the Plasma Concentrations of the Various Soluble Co-Inhibitory Immune Checkpoints before and after ART
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
List of Abbreviations
3TC | lamivudine |
AIDS | acquired immunodeficiency syndrome |
ART | antiretroviral therapy |
CTLA-4 | cytotoxic T-lymphocyte-associated protein 4 |
EFV | efavirenz |
HIV | Human immunodeficiency virus |
ICM | immune checkpoint molecules |
IFN-γ | interferon gamma |
IL | interleukin |
IQR | interquartile range |
LAG-3 | lymphocyte-activation gene 3 protein |
mAb | monoclonal antibody |
ng | nanogram |
PD-1 | programmed cell death protein 1 |
PD-L1 | programmed cell death protein ligand 1 |
pg | picogram |
PLWH | people living with HIV |
sICM | soluble immune checkpoint molecules |
TDF | tenofovir disoproxil fumarate |
TIM-3 | T cell immunoglobulin and mucin-domain 3 |
Tregs | regulatory T cells |
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Variable | PLWH before ART N = 68 | PLWH at 12 Months N = 68 | p-Value |
---|---|---|---|
CD4 count (cells/mm3) | 184 (74–317) * | 432 (245–582) | <0.0001 |
CD4 percentage (%) | 11.07 (6.47–18.59) * | 20.22 (13.24–31.01) | <0.0001 |
CD4:CD8 ratio | 0.23 (0.09–0.42) * | 0.48 (0.28–0.85) | <0.0001 |
HIV VL (copies/mL) | 166,000 (27,000–560,000) | 50 | <0.0001 |
HIV VL (log) | 5.2 (4.2–5.7) | 1.7 | <0.0001 |
Variable | PLWH before ART N = 68 | PLWH at 12 Months N = 68 | Control N = 15 | p-Value | |
---|---|---|---|---|---|
Pre-ART vs. Controls | On ART vs. Controls | ||||
CTLA-4 | 316.84 (106.92–622.97) | 342.50 (93.22–639.99) | 0.74 (0.73–1323.79) | 0.0657 | 0.0367 |
LAG-3 | 213,191.10 (154,145.20–256,134.90) | 232,113.60 (178,068.40–319,052.60) | 4293.78 (162.81–45,602.51) | 0.0001 | 0.0001 |
PD-1 | 3486.50 (2013.10–6240.06) | 3571.70 (1670.56–6515.27) | 849.36 (154.96–1869.33) | 0.0011 | 0.0033 |
PD-L1 | 628.37 (270.09–1094.94) | 771.59 (235.26–1316.53) | 101.02 (33.26–294.59) | 0.0030 | 0.0017 |
TIM-3 | 3450.73 (2449.28–4884.63) | 2817.07 (2141.62–3762.79) | 128.14 (4.90–2936.02) | 0.0001 | 0.0011 |
Variable | Non-Users N = 20 | Tobacco Users N = 12 | p-Value |
---|---|---|---|
CTLA-4 | 315.91 (93.22–692.07) | 370.27 (152.30–779.56) | 0.3485 |
LAG-3 | 226,348.30 (179,752.60–277,634.30) | 203,324.00 (187,789.00–283,333.90) | 0.4381 |
PD-1 | 3289.34 (1490.30–5864.21) | 4082.90 (2221.17–7413.38) | 0.1959 |
PD-L1 | 568.52 (267.93–1281.22) | 776.14 (369.52–1259.48) | 0.3064 |
TIM-3 | 2565.10 (1932.08–3079.84) | 3330.80 (2693.80–3893.81) | 0.0169 |
CTLA-4 | LAG-3 | PD-1 | PD-L1 | TIM-3 | |
---|---|---|---|---|---|
CTLA-4 | 1.0 | ||||
LAG-3 | 0.450 (0.0001) | 1.0 | |||
PD-1 | 0.907 (<0.0001) | 0.463 (0.0001) | 1.0 | ||
PD-L1 | 0.895 (<0.0001) | 0.437 (0.0002) | 0.873 (<0.0001) | 1.0 | |
TIM-3 | 0.081 (0.5100) | −0.053 (0.6668) | 0.120 (0.3306) | 0.088 (0.4769) | 1.0 |
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Labuschagne Naidoo, R.-B.; Steel, H.C.; Theron, A.J.; Anderson, R.; Tintinger, G.R.; Rossouw, T.M. Persistently Elevated Expression of Systemic, Soluble Co-Inhibitory Immune Checkpoint Molecules in People Living with HIV before and One Year after Antiretroviral Therapy. Pathogens 2024, 13, 540. https://doi.org/10.3390/pathogens13070540
Labuschagne Naidoo R-B, Steel HC, Theron AJ, Anderson R, Tintinger GR, Rossouw TM. Persistently Elevated Expression of Systemic, Soluble Co-Inhibitory Immune Checkpoint Molecules in People Living with HIV before and One Year after Antiretroviral Therapy. Pathogens. 2024; 13(7):540. https://doi.org/10.3390/pathogens13070540
Chicago/Turabian StyleLabuschagne Naidoo, Robyn-Brooke, Helen C. Steel, Annette J. Theron, Ronald Anderson, Gregory R. Tintinger, and Theresa M. Rossouw. 2024. "Persistently Elevated Expression of Systemic, Soluble Co-Inhibitory Immune Checkpoint Molecules in People Living with HIV before and One Year after Antiretroviral Therapy" Pathogens 13, no. 7: 540. https://doi.org/10.3390/pathogens13070540