Background
Methods
Study population
Specimen collection, genotyping and measurement of immune activation markers
Statistical analysis
Results
Cohort characteristics and distribution of CD14 (C-260T) SNP
Patient characteristics
|
CD14 C-260T genotype
#
|
Total cohort (N = 84)*
| ||
---|---|---|---|---|
CC (n = 15)*
|
CT (n = 41)*
|
TT (n = 24)*
| ||
Age, years | 38 (32–48) | 41 (37–45) | 41 (36–48) | 41 (36–46) |
Gender, n (%) male | 13 (86.7%) | 33 (80.5%) | 17 (70.8%) | 67 (79.8%) |
Ethnicity, n (%)
| ||||
- Malay | 7 (46.7%) | 7 (17.1%) | 3 (12.5%) | 19 (22.6%) |
- Chinese | 7 (46.7%) | 28 (68.3%) | 19 (79.2%) | 56 (66.7%) |
- Indian | 1 (6.7%) | 6 (14.6%) | 2 (8.3%) | 9 (10.7%) |
Baseline CD4 T-cell count, cells/μl | 30 (8–253) | 106 (13–223) | 60 (22–197) | 63 (16–228) |
Current CD4 T-cell count, cells/μl | 300 (155–450) | 386 (286–536) | 468 (292–631) | 387 (271–547) |
Current CD4:CD8 ratio | 0.36 (0.17–0.55) | 0.54 (0.33–0.73) | 0.59 (0.28–0.79) | 0.51 (0.28–0.74) |
Baseline HIV RNA, copies/ml | 163693 (59611–559681) | 137600 (50158–316679) | 105659 (33069–404288) | 136423 (52214–398660) |
Duration on ARV, years | 2 (1–6) | 5 (3–10) | 7 (2–10) | 4 (1–8) |
Current ARV regimen, n (%)
| ||||
- NNRTI-based | 13 (86.7%) | 36 (87.8%) | 21 (87.5%) | 74 (88.1%) |
- PI-based | 2 (13.3%) | 5 (12.2%) | 3 (12.5%) | 10 (11.9%) |
Previous abacavir use, n (%) | 1 (2.4%) | 1 (1.1%) | ||
Previous PI use, n (%) | 3 (7.3%) | 3 (3.6%) | ||
Positive hepatitis C antibody, n (%) | 0 (0.0%) | 0 (0.0%) | 1 (4.2%) | 2 (2.4%) |
Positive hepatitis B surface antigen, n (%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
Smoking, n (%) | ||||
- Never | 9 (60.0%) | 24 (58.5%) | 12 (50.0%) | 46 (54.8%) |
- Former | 2 (13.3%) | 4 (9.8%) | 4 (16.7%) | 10 (11.9%) |
- Current | 4 (26.7%) | 13 (31.7%) | 8 (33.3%) | 28 (33.3%) |
Framingham risk score, % | 5.85 (1.88–11.45) | 5.05 (2.93–8.63) | 4.75 (2.23–14.80) | 5.00 (2.75–11.05) |
Body mass index, kg/m2
| 22.3 (19.8–25.1) | 22.6 (21.4–25.4) | 24.1 (20.8–26.2) | 23.0 (21.2–25.5) |
Family history CVD, n (%) | 1 (6.7%) | 7 (17.1%) | 0 (0.0%) | 8 (9.5%) |
Diabetes, n (%) | 0 (0.0%) | 1 (2.4%) | 2 (8.3%) | 4 (4.8%) |
Hypertension, n (%) | 9 (60.0%) | 14 (34.1%) | 8 (33.3%) | 32 (38.1%) |
Fasting glucose, mmol/L | 4.8 (4.5–5.5) | 5.2 (4.9–5.5) | 5.3 (4.7–5.8) | 5.1 (4.7–5.6) |
Total cholesterol, mmol/L | 5.4 (4.2–5.8) | 5.2 (4.7–6.2) | 5.2 (4.8–5.6) | 5.2 (4.6–5.8) |
LDL, mmol/L | 2.8 (2.5–3.6) | 3.1 (2.5–3.9) | 3.1 (2.6–3.5) | 3.0 (2.5–3.6) |
HDL, mmol/L | 1.2 (0.9–1.5) | 1.2 (1.0–1.5) | 1.1 (0.9–1.3) | 1.2 (0.9–1.4) |
Triglycerides, mmol/L | 2.0 (1.4–2.8) | 1.8 (1.5–2.3) | 2.1 (1.5–3.3) | 1.9 (1.4–2.5) |
Increased cIMT, (>0.7 mm), n (%) | 3 (20.0%) | 13 (31.7%) | 6 (25.0%) | 23 (27.4%) |
TLR4 frequency, n (%) | ||||
- TLR4 Asp299Gly (c.896A > G) (rs4986790) | 1 (2.4%) | 1 (1.1%) | ||
- TLR4 Thr399Ile (c.1196C > T) (rs2569190) | 1 (2.4%) | 1 (1.1%) |
Association between CD14 C-260T SNP and markers of monocyte activation and systemic inflammation
CC/CT (n = 56)
*
|
TT (n = 24)
*
|
p
|
p
Δ
| |
---|---|---|---|---|
Immune activation and inflammatory markers
| ||||
Log sCD14 | 6.20 (6.11–6.28) | 6.24 (6.15–6.30) | 0.266§
| 0.188 |
Log sCD163 | 2.94 (2.84–3.07) | 3.03 (2.97 3.20) | 0.008§
| 0.013 |
Log hsCRP | -0.77 (-0.32 - -1.08) | -0.53 (-0.26 - -0.95) | 0.296§
| 0.232 |
Cardiovascular risk factors
| ||||
Body mass index, kg/m2
| 22.4 (20.9–25.2) | 23.9 (20.6–26.0) | 0.482§
| |
Fasting sugar, mmol/L | 5.0 (4.6–5.5) | 5.1 (4.6–5.8) | 0.298§
| |
Total cholesterol, mmol/L | 5.2 (4.6–6.0) | 5.1 (4.8–5.6) | 0.858§
| |
Triglyceride, mmol/L | 1.8 (1.4–2.3) | 2.0 (1.5–2.8) | 0.239§
| |
HDL, mmol/L | 1.24 (0.99–1.49) | 1.12 (0.90–1.31) | 0.087§
| |
LDL, mmol/L | 2.9 (2.5–3.8) | 3.1 (2.6–3.5) | 0.978§
| |
Age, years | 41 (36–46) | 41 (36–48) | 0.961§
| |
Male gender, % | 82.1% | 70.8% | 0.257
#
| |
Current smoker, % | 30.4% | 33.3% | 0.792
#
| |
Framingham risk score | 5.05 (2.80–9.08) | 4.75 (2.23–14.80) | 0.925§
|
Association between CD14 C-260T SNP and increased cIMT
Predictors
|
Co-efficient (95% confidence interval)
|
p-value
|
---|---|---|
Univariable model
| ||
Age, years | 0.007 (0.004, 0.011) | <0.001* |
Body mass index, kg/m2
| 0.006 (-0.005, 0.017) | 0.273 |
Total cholesterol, mmol/L | 0.015 (-0.021, 0.051) | 0.415 |
Triglyceride, mmol/L | 0.003 (-0.029, 0.029) | 0.985 |
HDL, mmol/L | -0.001 (-0.105, 0.103) | 0.984 |
LDL, mmol/L | 0.019 (-0.022, 0.060) | 0.369 |
Fasting glucose, mmol/L | -0.017 (-0.053, 0.020) | 0.366 |
Framingham score, % | 0.011 (0.006, 0.016) | <0.001 |
Baseline CD4 T-cell counts, per 100 cells/μl | -0.011 (-0.044, 0.022) | 0.527 |
Log baseline HIV RNA | -0.006 (-0.028, 0.016) | 0.585 |
Log current CD4 T-cell counts | 0.043 (-0.016, 0.104) | 0.151 |
Log sCD14 | 0.020 (-0.083, 0.123) | 0.700 |
Log sCD163 | -0.054 (-0.135, 0.027) | 0.190 |
Log hsCRP | 0.0005 (-0.025, 0.026) | 0.970 |
CD14 C-260T genotype; CC/CT vs TT | -0.013 (-0.099, 0.071) | 0.758 |
Multivariable model
| ||
Framingham score, % | 0.009 (0.004, 0.014) | <0.001 |
Log current CD4 T-cell counts | 0.038 (-0.033, 0.108) | 0.289 |
Log sCD163 | -0.084 (-0.182, 0.013) | 0.087 |