Association of High Ratio of CSF/Plasma HIV-1 RNA with Central Nervous System Co-Infection in HIV-1-Positive Treatment-Naive Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Data Collection
2.3. Laboratory Assessments
2.4. CNS Co-Infection Assessments
- Tuberculous meningitis: (i) The CSF with lymphocytic pleocytosis, low glucose, and elevated protein; (ii) the brain CT/MRI showing enhancement of the meninges and the periphery with the tuberculoma lesions; (iii) the culture or CSF smear or CSF-PCR; (iv) the successful response by a specific treatment. The diagnosis complied with (iii) or any two of the other three criteria.
- Toxoplasma meningitis should have been consistent at the same time: (i) progressive neurological deficits; (ii) contrast-enhancing mass lesion(s) on the CT/MRI; (iii) successful response within 2 weeks of the specific treatment.
- Cryptococcal meningitis needed to meet any one of these criteria: (i) visualizing the fungus in the CSF using India ink; (ii) detecting the cryptococcal antigen by the latex agglutination assay in the CSF; (iii) positive CSF culture for C. neoformans.
- Diagnosis of neurosyphilis should have been consistent at the same time: (i) epidemiological history; (ii) clinical manifestations; (iii) positive serum TPPA; (iv) CSF leukocyte count of ≥20 × 106/L; CSF protein of ≥500 mg/L; (v) CSF TPPA positive.
- Viral encephalitis included CMV (cytomegalovirus) and JC virus (JCV). Diagnosis of CMV encephalitis via clinical appearance, positive PCR in CSF, and other pathology was excluded. Diagnosis of Progressive Multifocal Leukoencephalopathy, which is caused by JCV, depends on the evidence of JCV-deoxyribonucleic acid (JCV-DNA) in CSF and compatible clinical-radiological picture.
- Multiple co-infections referred to the combination of more than two types of co-infection
- Detection of co-infectious pathogens mentioned in our manuscript by Next-Generation Sequencing (NGS) testing.
2.5. Statistical Methods
3. Results
Multivariate Analyses between the HRR and CNS Co-Infection
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CNI Group (N = 98) | Non-CNI Group (N = 97) | p-Value | |
---|---|---|---|
Age (mean ± SD) | 46.74 ± 12.65 | 49.74 ± 16.15 | 0.239 |
Male gender, n (%) | 76(77.55) | 75(77.32) | 0.969 |
Disease characteristics | |||
CD 4 (cell per µL), median (IQR) | 20 (39–72) | 41 (19–106) | 0.365 |
Ratio of CD4/CD8, median (IQR) | 0.08 (0.13–0.20) | 0.145 (0.08–0.24) | 0.326 |
Serum albumin (mean ± SD) | 35.63 ± 6.84 | 33.97 ± 6.38 | 0.072 |
Plasma HIV RNA (Log copies/mL), median (IQR) | 5.86 (5.50–6.27) | 5.69 (5.19–6.19) | 0.158 |
CSF HIV RNA (log copies/mL), median (IQR) | 4.78 (3.67–5.55) | 3.98 (3.10–4.65) | <0.001 |
CSF/plasma HIV RNA ratio, (mean ± SD) | 0.82 ± 0.22 | 0.71 ± 0.19 | <0.001 |
CSF protein (mg/L), median (IQR) | 594.86 (362.96–978.64) | 359.01 (310.93–451.22) | <0.001 |
CSF chloride (mmol/L), mean ± SD | 121.0 ± 8.75 | 124.42 ± 4.36 | 0.001 |
CSF glucose, (mmol/L), median (IQR) | 3.19 (2.44–3.60) | 3.66 (3.23–4.33) | <0.001 |
CSF white blood cells (cell per µL), median (IQR) | 5 (0–84) | 1 (0–4) | <0.001 |
Variables | CNS Co-Infection (N = 98) | TBM (N = 30) | CM (N = 18) | TM (N = 11) | VE (N = 14) | NS (N = 6) | MI (N = 19) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | |
CSF/plasma HRR | ||||||||||||||
<1.00 | ||||||||||||||
≥1.00 | 5.19 (2.02–13.33) | 0.001 | 6.50 (2.08–20.25) | 0.001 | 7.58 (2.10–27.32) | 0.002 | 3.37 (0.59–19.21) | 0.171 | 4.13 (0.90–18.92) | 0.067 | 3.03 (0.30–30.27) | 0.344 | 4.04 (1.02–16.04) | 0.047 |
CSF/plasma HRR | 13.78 (3.27–58.13) | <0.001 | 8.92 (1.11–71.19) | 0.039 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Age | 0.98 (0.96–1.00) | 0.153 | 0.98 (0.96–1.01) | 0.348 | 0.98 (0.95–1.02) | 0.478 | 0.99 (0.95–1.03) | 0.785 | 0.99 (0.96–1.03) | 0.855 | 0.94 (0.88–1.00) | 0.073 | 0.99 (0.95–1.02) | 0.532 |
Male | 0.98 (0.50–1.93) | 0.969 | 1.24 (0.48–3.16) | 0.654 | 1.31 (0.42–4.08) | 0.640 | 1.27 (0.31–5.23) | 0.733 | 0.93 (0.23–3.63) | 0.917 | NA | NA | 0.63 (0.17–2.39) | 0.507 |
CD 4 count (log 10 cell per µL) | 0.71 (0.39–1.28) | 0.262 | 0.79 (0.35–1.77) | 0.572 | 0.47 (0.17–1.36) | 0.165 | 0.76 (0.21–2.78) | 0.683 | 1.21 (0.39–3.76) | 0.738 | 1.89 (0.32–10.85) | 0.475 | 0.44 (0.15–1.28) | 0.133 |
Ratio of CD4/CD8 | 0.25 (0.03–1.79) | 0.170 | 0.30 (0.01–5.32) | 0.418 | 0.00 (0.00–0.98) | 0.050 | 0.03 (0.00–9.13) | 0.234 | 1.12 (0.03–35.72) | 0.947 | NA | NA | 0.89 (0.03–20.61) | 0.946 |
Serum albumin | 1.03 (0.99–1.08) | 0.087 | 1.02 (0.95–1.08) | 0.550 | 1.04 (0.97–1.11) | 0.183 | 1.04 (0.94–1.15) | 0.389 | 1.04 (0.96–1.14) | 0.281 | 1.06 (0.93–1.21) | 0.324 | 1.04 (0.96–1.13) | 0.304 |
Plasma HIV RNA (Log copies/mL) | 1.25 (0.90–1.73) | 0.167 | 1.25 (0.78–1.99) | 0.346 | 1.79 (0.88–3.64) | 0.103 | 1.225 (0.63–2.39) | 0.551 | 0.87 (0.48–1.58) | 0.666 | 0.65 (0.30–1.42) | 0.284 | 1.89 (0.93–3.84) | 0.076 |
CSF HIV RNA concentration (Log copies/mL) | 1.71 (1.32–2.20) | <0.001 | 1.59 (1.11–2.29) | 0.011 | 2.92 (1.67–5.10) | <0.001 | 1.55 (0.84–2.87) | 0.158 | 1.34 (0.79–2.26) | 0.266 | 1.34 (0.61–2.92) | 0.457 | 2.27 (1.36–3.79) | 0.002 |
CSF protein (mg/L) | 1.003 (1.002–1.004) | <0.001 | 1.003 (1.001–1.004) | <0.001 | 1.002 (1.001–1.004) | 0.006 | 1.002 (1.002–1.004) | 0.014 | 1.002 (1.000–1.004) | 0.027 | 1.003 (1.000–1.005) | 0.021 | 1.003 (1.001–1.004) | 0.001 |
CSF chloride(mmol/L) | 0.92 (0.88–0.97) | <0.001 | 0.91 (0.84–0.97) | 0.011 | 0.86 (0.78–0.96) | 0.009 | 0.96 (0.83–1.10) | 0.574 | 0.93 (0.82–1.05) | 0.271 | 0.96 (0.79–1.17) | 0.744 | 0.86 (0.79–0.94) | 0.001 |
CSF glucose(mmol/L) | 0.62 (0.47–0.82) | 0.001 | 0.59 (0.38–0.89) | 0.013 | 0.31 (0.16–0.61) | 0.001 | 0.29 (0.10–0.87) | 0.027 | 0.54 (0.25–1.17) | 0.122 | 0.18 (0.04–0.66) | 0.010 | 0.74 (0.45–1.22) | 0.249 |
CSF white blood cells (cell per µL) | 1.05 (1.01–1.09) | 0.005 | 1.05 (0.99–1.10) | 0.061 | 1.10 (1.03–1.18) | 0.005 | 1.08 (0.99–1.17) | 0.053 | 1.04 (1.00–1.08) | 0.035 | 1.05 (0.99–1.11) | 0.069 | 1.07 (1.00–1.14) | 0.039 |
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Liu, Q.; Tao, W.; Yang, H.; Wu, Y.; Yu, Q.; Liu, M. Association of High Ratio of CSF/Plasma HIV-1 RNA with Central Nervous System Co-Infection in HIV-1-Positive Treatment-Naive Patients. Brain Sci. 2022, 12, 791. https://doi.org/10.3390/brainsci12060791
Liu Q, Tao W, Yang H, Wu Y, Yu Q, Liu M. Association of High Ratio of CSF/Plasma HIV-1 RNA with Central Nervous System Co-Infection in HIV-1-Positive Treatment-Naive Patients. Brain Sciences. 2022; 12(6):791. https://doi.org/10.3390/brainsci12060791
Chicago/Turabian StyleLiu, Qian, Wendan Tao, Honghong Yang, Yushan Wu, Qing Yu, and Min Liu. 2022. "Association of High Ratio of CSF/Plasma HIV-1 RNA with Central Nervous System Co-Infection in HIV-1-Positive Treatment-Naive Patients" Brain Sciences 12, no. 6: 791. https://doi.org/10.3390/brainsci12060791
APA StyleLiu, Q., Tao, W., Yang, H., Wu, Y., Yu, Q., & Liu, M. (2022). Association of High Ratio of CSF/Plasma HIV-1 RNA with Central Nervous System Co-Infection in HIV-1-Positive Treatment-Naive Patients. Brain Sciences, 12(6), 791. https://doi.org/10.3390/brainsci12060791