Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Participants’ Demographic and Clinical Features
3.2. Antiretroviral Naïve and Treated Participants
3.3. Blood–Brain Barrier Impairment and CSF Biomarkers
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | cART-Naïve | cART-Treated | |
---|---|---|---|
n | 147 | 317 | |
Age | Years | 44.1 (38.0–51.7) | 49.2 (42.8–57.5) |
Sex | Female | 41 (27.9) | 88 (27.8) |
BMI | Kg/m2 | 18.5 (12.8–21.7) | 23.9 (22.2–25.8) |
Ancestry | European | 119 (84.4) | 216 (86.4) |
African | 14 (9.9) | 28 (11.2) | |
South American | 6 (4.3) | 6 (2.4) | |
Other | 2 (1.4) | 0 | |
Risk Factors | Males who have sex with males | 44 (33.6) | 66 (28.1) |
Heterosexuals | 41 (31.3) | 60 (25.5) | |
Intravenous drug users | 24 (18.3) | 80 (34.0) | |
Other | 6 (4.6) | 6 (2.6) | |
Unknown | 15 (11.5) | 23 (9.8) | |
Comorbidities | Liver cirrhosis | 6 (4.2) | 27 (10.9) |
Psychiatric disorders | 25 (19.4) | 46 (19.0) | |
Past syphilis | 30 (21.4) | 54 (22.0) | |
Chronic HCV | 24 (16.8) | 70 (28.2) | |
Chronic HBV | 14 (9.9) | 32 (12.9) | |
Toxoplasma positive serology | 15 (31.2) | 29 (42.0) | |
Active smoking | 45 (30.7) | 89 (28.0) |
Characteristics | ART-Naïve (n = 147) | ART-Treated (n = 317) | |
---|---|---|---|
Diagnosis | Asymptomatic/control | 8 (5.8) | 64 (23.7) |
Primary infection | 1 (0.7) | – | |
Late presentation | 77 (55.8) | 17 (6.3) | |
Other CNS disorders | 11 (8.0) | 44 (16.3) | |
CNS opportunistic infections | 19 (13.8) | 34 (12.6) | |
HIV-related encephalitis/escape/rebound | 2 (1.4) | 7 (2.6) | |
HAND | 14 (10.1) | 77 (28.5) | |
White matter hyperintensity | 2 (1.4) | 11 (4.1) | |
Syphilis | 1 (0.7) | 13 (4.8) | |
Neuro syphilis | 3 (2.2) | 3(1.1) | |
RMN | White matter hyperintensities | 87 (64.4) | 150 (68.8) |
Therapy | PI | – | 41 (12.9) |
INSTI | – | 88 (28) | |
MVC | – | 16 (5) | |
NNRTI | – | 55 (17.4) | |
Number of drugs | – | 3 |
Characteristics | ART-Naïve (n = 147) | ART-Treated (n = 317) | p Values |
---|---|---|---|
Nadir CD4+ (cell/mm3) | 49 (20–118) | 97 (26.5–208) | 0.002 |
CD4+ (cell/mm3) | 57 (23–117) | 366.5 (154.25–620.5) | <0.001 |
HIV DNA (copies/106 PBMCs) | 478.5 (138.25–2462.5) | 123 (29–395) | 0.002 |
Serum HIV RNA (log10 cps/mL) | 5.42 (4.93–5.95) | 1.28 (0.42–1.91) | <0.001 |
CSF HIV RNA (log10 cps/mL) | 3.88 (3.07–4.7) | 1.28 (0.04–2.08) | <0.001 |
HIV duration (months) | 1.23 (0.43–125.63) | 143.37 (44.98–225.96) | <0.001 |
Viral suppression (months) | 0 (0–0) | 18 (3.8–73) | <0.001 |
CSF cells | 0 (0–3) | 0 (0–2) | 0.266 |
CSF proteins | 49 (39–68.25) | 48 (38–63) | 0.557 |
CSF glucose | 50 (45–57) | 48 (51–63) | <0.001 |
Serum HIV RNA < 50 cps/mL | 1 (0.7) | 196 (70.8) | <0.001 |
CSF HIV RNA < 50 cps/mL | 5 (3.6) | 178 (63.3) | <0.001 |
NADIR CD4 < 200 cells/mm3 | 117 (84.2) | 164 (71.3) | 0.005 |
BBB impairment | 52 (35.4) | 72 (22.7) | 0.005 |
CSAR | 6.2 (4.3–8.7) | 5.6 (4.1–7.6) | 0.119 |
Intrathecal IgG Synthesis | 0 (0–25) | 0 (0–20) | 0.280 |
t–Tau | 165 (96–293) | 222 (129–350) | 0.045 |
p–Tau | 33 (25–41) | 37 (27–51) | 0.040 |
Aβeta42 | 962 (704–1142) | 919 (736–1171) | 0.901 |
S100Beta | 145 (48–260) | 129 (70.25–219.5) | 0.758 |
Neopterin | 2.9 (1.4–5.7) | 0.9 (0.5–1.9) | <0.001 |
JCV DNA+ | 8 (5.6) | 17 (5.1) | 1.000 |
EBV DNA+ | 32 (22.3) | 32 (10.1) | 0.001 |
CMV DNA+ | 8 (5.6) | 5 (1.5) | 0.030 |
Characteristics | Naïve Features | cART-Treated Features | ||||
---|---|---|---|---|---|---|
Intact BBB | BBBi | p Values | Intact BBB | BBBi | p Values | |
n | 95 (64.6) | 52 (35.4) | – | 245 (77.3) | 72 (22.7) | – |
Female sex | 31 (32.6) | 10 (19.2) | 0.088 | 75 (30.6) | 13 (18.1) | 0.037 |
Age | 46 (39–52) | 41 (37–49) | 0.034 | 49 (43–57) | 48 (42–56) | 0.854 |
CD4+ (cell/mm3) | 47 (20–110) | 72 (36–218) | 0.132 | 371 (155–628) | 357 (145–593) | 0.910 |
Nadir CD4+ (cell/mm3) | 46 (15–107) | 71 (26–149) | 0.089 | 95 (25–202) | 100 (31–229) | 0.283 |
Nadir CD4 < 200 cells/mm3 | 78 (87.6) | 39 (78.0) | 0.152 | 132 (73.3) | 32 (64.0) | 0.218 |
Serum HIV RNA (Log10 cps/mL) | 5.4 (4.9–5.9) | 5.6 (4.9–6.0) | 0.098 | <1.28 (<1.28–1.80) | <1.28 (<1.28–2.32) | 0.598 |
Serum HIV RNA < 50 cps/mL | 1 (1.1) | 0 (0) | 1.00 | 157 (72.7) | 39 (63.9) | 0.204 |
HIV DNA (copies/106 PBMCs) | 478 (76–2324) | 903 (160–12064) | 0.291 | 91 (<50–362) | 147 (70–829) | 0.160 |
HIV duration (months) | – | – | – | 143 (45–226) | 142 (42–225) | 0.929 |
Viral suppression (months) | – | – | – | 17 (2.5–65) | 29 (9–95) | 0.115 |
History of CNS opportunistic infections | 6 (6.3) | 13 (25) | 0.002 | 18 (7.3) | 16 (22.2) | 0.001 |
Receiving NNRTIs | – | – | – | 38 (15.5) | 17 (23.6) | 0.114 |
Receiving PIs | – | – | – | 31 (12.7) | 10 (13.9) | 0.842 |
Receiving INSTIs | – | – | – | 75 (30.9) | 13 (18.3) | 0.050 |
CSF cells ≥ 5/mm3 | 12 (13) | 21 (41.2) | <0.001 | 20 (9.5) | 17 (27.9) | 0.001 |
CSF proteins | 40 (34–49) | 75 (56–90) | <0.001 | 43 (34–52) | 81 (66–107) | <0.001 |
CSF glucose | 51 (45–58) | 48 (42–54) | 0.022 | 57 (52–63) | 56 (50–65) | 0.940 |
CSF HIV RNA (Log10 cps/mL) | 3.71 (2.82–4.39) | 4.36 (3.49–5.09) | 0.002 | <1.28 (<1.28–2.03) | 1.53 (<1.28–2.66) | 0.029 |
CSF HIV RNA < 50 cps/mL | 4 (4.3) | 1 (2.1) | 0.660 | 143 (65.3) | 35 (56.5) | 0.233 |
CSAR | 5.0 (3.8–6.0) | 9.6 (8.3–12.8) | <0.001 | 4.9 (3.8–6.2) | 10.4 (8.8–13.4) | <0.001 |
Intrathecal IgG Synthesis (%) | 38 (40.4) | 15 (29.4) | 0.210 | 76 (33.8) | 17 (25.8) | 0.234 |
tau | 134 (93–306) | 173 (136–285) | 0.282 | 225 (134–344) | 212 (113–403) | 0.865 |
p–Tau | 31 (24–41) | 34 (27–42) | 0.423 | 36 (26–51) | 39 (29–50) | 0.648 |
Aβeta42 | 925 (734–1144) | 1017 (580–1149) | 0.947 | 918 (726–1165) | 950 (752–1284) | 0.665 |
S100Beta | 151 (55–281) | 102 (38–229) | 0.410 | 121 (71–202) | 178 (60–351) | 0.269 |
Neopterin | 2.52 (1.19–4.80) | 3.42 (2.10–9.80) | 0.029 | 0.88 (0.50–1.70) | 1.38 (0.50–3.40) | 0.048 |
JCV DNA+ | 3 (3.2) | 5 (9.6) | 0.131 | 10 (4.1) | 7 (9.7) | 0.075 |
EBV DNA+ | 16 (16.8) | 16 (30.8) | 0.061 | 19 (7.8) | 13 (18.1) | 0.015 |
CMV DNA+ | 1 (1.1) | 7 (13.5) | 0.003 | 3 (1.2) | 2 (2.8) | 0.319 |
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Caligaris, G.; Trunfio, M.; Ghisetti, V.; Cusato, J.; Nigra, M.; Atzori, C.; Imperiale, D.; Bonora, S.; Di Perri, G.; Calcagno, A. Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers. Diagnostics 2021, 11, 867. https://doi.org/10.3390/diagnostics11050867
Caligaris G, Trunfio M, Ghisetti V, Cusato J, Nigra M, Atzori C, Imperiale D, Bonora S, Di Perri G, Calcagno A. Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers. Diagnostics. 2021; 11(5):867. https://doi.org/10.3390/diagnostics11050867
Chicago/Turabian StyleCaligaris, Giulia, Mattia Trunfio, Valeria Ghisetti, Jessica Cusato, Marco Nigra, Cristiana Atzori, Daniele Imperiale, Stefano Bonora, Giovanni Di Perri, and Andrea Calcagno. 2021. "Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers" Diagnostics 11, no. 5: 867. https://doi.org/10.3390/diagnostics11050867
APA StyleCaligaris, G., Trunfio, M., Ghisetti, V., Cusato, J., Nigra, M., Atzori, C., Imperiale, D., Bonora, S., Di Perri, G., & Calcagno, A. (2021). Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers. Diagnostics, 11(5), 867. https://doi.org/10.3390/diagnostics11050867