Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV
Abstract
:1. Introduction
2. Participants and Methods
2.1. Study Design, Participants, and Outcome Measures
2.2. Biomarker Quantification
2.3. Statistical Methods
3. Results
3.1. Study Participant Characteristics at Entry
3.2. Multivariable Ferritin Associations with Global NCI and Neurocognitive Performance and Interaction Effects by Sex
3.3. FTL and FTH1 Associations with Neurocognitive Domain Test Scores
3.4. FTL and FTH1 Associations with Longitudinal Neurocognitive Performance
3.5. Ferritin Associations with Inflammation, Lipid Peroxidation, and Anemia
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Neurocognitively Normal (N = 237) | Neurocognitively Impaired 1 (N = 82) |
---|---|---|
Age, mean (SD) | 51.4 (6.9) | 53.7 (8.3) |
Sex, % female | 17.3 | 24.4 |
Non-Hispanic Black 2, % | 31.6 | 20.7 4 |
Hispanic 2, % | 20.7 | 36.6 ** |
Efavirenz use, % | 51.5 | 39.0 5 |
Nadir CD4+ T-cells/µL, median (IQR) | 192 (67, 314) | 237 (80, 347) |
HIV RNA < 200 copies/mL, % | 95.7 | 96.3 |
Anemia, % | 10.5 | 12.7 |
HCV seropositive, % | 2.53 | 8.54 * |
≥2 Comorbidities 3, % | 32.5 | 47.6 * |
Biomarker | All PWH (N = 324) Median (IQR) | Men (N = 263) Median (IQR) | Women (N = 61) Median (IQR) |
---|---|---|---|
Serum FTH1, ng/mL | 289 (199, 499) | 311 (197, 497) | 277 (136, 526) |
Serum FTL, ng/mL | 12.2 (7.7, 22.1) | 12.4 (7.7, 22.4) | 11 (7.2, 19.6) |
Urinary 15-series F2-IsoPs 1, ng/mg Creatinine | 57 (32, 84) | 56 (31, 84) | 60 (43, 78) |
Urinary 5-series F2-IsoPs 1, ng/mg Creatinine | 71 (34, 109) | 66 (33, 110) | 71 (38, 98) |
Biomarker | IL-6 (N = 324) rho (p) | sTNFR-II (N = 324) rho (p) | sCD163 (N = 324) rho (p) | 15-F2-IsoPs (N = 310) rho (p) | 5-F2-IsoPs (N = 310) rho (p) |
---|---|---|---|---|---|
FTH1 | |||||
All PWH | −0.007 (0.91) | −0.043 (0.45) | 0.0005 (0.99) | −0.061 (0.28) | 0.033 (0.55) |
Women | −0.085 (0.52) | 0.128 (0.33) | 0.157 (0.23) | −0.290 (0.02) | −0.181 (0.16) |
Men | 0.013 (0.83) | −0.085 (0.17) | −0.041 (0.51) | 0.016 (0.80) | 0.089 (0.15) |
FTL | |||||
All PWH | −0.026 (0.64) | −0.078 (0.16) | −0.050 (0.37) | −0.017 (0.77) | 0.048 (0.39) |
Women | 0.018 (0.89) | 0.086 (0.51) | 0.024 (0.85) | −0.471 (<0.001) | −0.347 (<0.01) |
Men | −0.030 (0.63) | −0.117 (0.06) | −0.066 (0.29) | 0.094 (0.14) | 0.134 (0.03) |
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Kaur, H.; Alluri, R.K.; Wu, K.; Kalayjian, R.C.; Bush, W.S.; Palella, F.J.; Koletar, S.L.; Hileman, C.O.; Erlandson, K.M.; Ellis, R.J.; et al. Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV. Antioxidants 2024, 13, 1042. https://doi.org/10.3390/antiox13091042
Kaur H, Alluri RK, Wu K, Kalayjian RC, Bush WS, Palella FJ, Koletar SL, Hileman CO, Erlandson KM, Ellis RJ, et al. Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV. Antioxidants. 2024; 13(9):1042. https://doi.org/10.3390/antiox13091042
Chicago/Turabian StyleKaur, Harpreet, Ravi K. Alluri, Kunling Wu, Robert C. Kalayjian, William S. Bush, Frank J. Palella, Susan L. Koletar, Corrilynn O. Hileman, Kristine M. Erlandson, Ronald J. Ellis, and et al. 2024. "Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV" Antioxidants 13, no. 9: 1042. https://doi.org/10.3390/antiox13091042