Baseline conditions
Sixty-one treatment-naive male patients with HIV in the Public and Health Clinic Centre of Chengdu from October 1, 2012, to December 31, 2017, were divided into three groups according to their baseline CD4 + T cell count: there were 26, 12, and 23 patients in the < 200, 200 to 350, and > 350 cell/µl groups, respectively. There were 42 cases of infection through homosexual contact, 13 cases of infection through heterosexual contact and 5 cases involving both types of sexual contact. The general information, baseline immunity and virological indicators, and lipid metabolism parameters of 61 patients are shown in Table 1.
Table 1
Baseline information of male patients with HIV (n = 61)
variable
|
χ±SD or cases(%)
|
range
|
age(years)
|
32.05 ± 8.38
|
20 ~ 58
|
gender(male,%)
|
61(100%)
|
|
infection duration (months)
|
11.16 ± 1.19
|
1 ~ 86
|
T lymphocyte subsets
|
|
|
CD3 + count (cells/ul)
|
1433.98 ± 595.35
|
470 ~ 3074
|
CD3 + CD4 + count (cells/ul)
|
313.87 ± 118.473
|
54 ~ 499
|
CD3 + CD4 + percentage (%)
|
19.78 ± 6.83
|
1.40 ~ 43.40
|
CD3 + CD8 + count (cells/ul)
|
1119.70 ± 605.0
|
360 ~ 2456
|
CD3 + CD8 + percentage (%)
|
69.97 ± 13.80
|
36.13 ~ 97.20
|
*Virus load of HIVRNA
|
41772.77 ± 10.38
|
895.00 ~ 505987.00
|
metabolic parameters
|
|
|
TG (mmol/L)
|
1.68 ± 1.23
|
0.39 ~ 16.81
|
TC (mmol/L)
|
4.20 ± 0.72
|
2.38 ~ 6.09
|
LDL-c (mmol/L)
|
2.61 ± 0.68
|
0.92 ~ 4.71
|
HDL-c (mmol/L)
|
1.12 ± 0.24
|
0.57 ~ 1.77
|
UA (µmol/L)
|
310.72 ± 68.65
|
143 ~ 506
|
anthropometric parameters
|
|
|
Body weight (kg)
|
62.41 ± 10.53
|
46 ~ 85
|
Body mass index (kg/m2)
|
21.38 ± 2.82
|
16.80 ~ 28.20
|
Body fat percentage (%)
|
15.99 ± 6.32
|
3 ~ 28.4
|
Body fat weight (kg)
|
10.40 ± 5.33
|
1.4 ~ 22.10
|
Body nonfat weight (kg)
|
51.82 ± 6.67
|
35.8 ~ 64.7
|
Baseline body mass status
|
|
|
Body mass index < 18 kg/m2
|
3 (4.92)
|
|
24Kg/m2 ≥ Boby mass index ≥ 18 kg/m2
|
49 (80.33)
|
|
Body mass index˃24 kg/m2
|
9 (14.75)
|
|
Note: Abbreviation: TG, triglyceride. TC, total cholesterol. LDL-c, low-density lipoprotein cholesterol. HDL-c, high-density lipoprotein cholesterol. UA, uric acid. *refers to logarithmic transformation before statistical analysis for nonnormally distributed data. |
Effectiveness of ART with the TDF plus 3TC plus EFV regimen
In 61 patients, the average CD4 + T cell count (Fig. 1A) gradually increased from 319.80 cell/µl at baseline to 464.85 cell/µl at 96 weeks after ART, and the average viral load (Fig. 1B) decreased rapidly from 49846.32 IU/ml at baseline to undetectable levels (measured by a high-precision detection method) at 72 weeks. The percentage of viral load reaching undetectable levels (Fig. 1C) ranged from 21.31% at 12 weeks to 100.00% at 72 weeks.
Long-term dynamic changes in anthropometric parameters after treatment with TDF + 3TC + EFV
The body weight (Fig. 2A) and lean body mass weight (Fig. 2B) of patients did not change significantly over the 144 weeks (all P > 0.05). The body mass index (Fig. 2C), body fat weight (Fig. 2D) and body fat percentage (Fig. 2E) of patients gradually increased over 144 weeks (all P < 0.05), and the increments were 0.95 kg/m2, 2.7 kg, and 4.31%, respectively; body fat weight and body fat percentage, in particular, showed considerable increases.
Long-term dynamic changes in lipid and purine metabolism parameters after treatment with TDF + 3TC + EFV
TC, LDL-c, HDL-c, TG and UA levels (Fig. 3A, 3B, 3C, 3D and 5A) all gradually increased with prolonged ART, but the increases were small, and only the increases in TC levels (Fig. 3A) and HDL-c levels (Fig. 3C) were statistically significant (P = 0.0007, 0.000, respectively). Compared with baseline, there were significant differences in TC levels at 96 and 144 weeks (Fig. 3A) and in HDL-c levels at 48, 96 and 144 weeks (Fig. 3C) (P = 0.002, 0.0329, 0.0004, 0.0001, 0.0157, respectively). There were no significant differences in LDL-c (Fig. 3B), TG (Fig. 3D) or UA levels (Fig. 5A) between different time points compared with baseline (all P > 0.05).
The percentages of hypercholesterolemia (Fig. 4A), hyper LDL cholesterolemia (Fig. 4B) and hypertriglyceridemia (Fig. 4D) all gradually increased, but the increases were not significant (all P > 0.05). In contrast, the percentage of hypo-HDL cholesterolemia (Fig. 4C) gradually decreased with prolonged ART, and a significant difference was found from baseline to 144 weeks (Fig. 4C) (P = 0.0007) and at 24, 48, 96, 144 weeks compared with baseline (Fig. 4C) (P = 0.026, 0.014, 0.001, 0.036, respectively). The percentage of hyperuricemia (Fig. 5B) slightly decreased with the extension of the HAART treatment time, but this decrease was not significant (P > 0.05).
Effect of baseline CD4 + cell count on lipid and purine metabolic parameters after treatment with TDF + 3TC + EFV
The lower the CD4 + cell count at baseline was, the higher the TG levels (Fig. 6D) and the lower the TC (Fig. 6A), LDL-c (Fig. 6B), HDL-c (Fig. 6C) and UA levels (Fig. 7) were; moreover, these changes were maintained throughout the follow-up period after ART treatment. However, there was no significant difference in the change from baseline to 96 weeks between the three different CD4 + cell count groups (all P > 0.05). The difference of the LDL-c levels (Fig. 6B) at baseline was significant between the three different CD4 + cell count groups (P = 0.0457). TC levels (Fig. 6A) and HDL-c levels (Fig. 6C) all gradually increased along with prolonged ART regardless of the CD4 + cell count at baseline.
The risk factors of lipid and purine metabolic parameters
According to Spearman correlation analysis, nonalcoholic fatty liver disease, age, body weight, BMI, body fat weight, and body fat percentage were all positively correlated with TC, TG and LDL-c levels; lean body mass weight was positively correlated with LDL-c levels; and follow-up duration was positively correlated with TC and HDL-c levels. In contrast, nonalcoholic fatty liver disease, body weight, BMI, body fat weight, body fat percentage and lean body mass weight were all negatively correlated with HDL-c levels (Table 2). Based on multiple stepwise regression analysis, the risk factors for TC levels included body weight, age, lean body mass weight and follow-up duration, for TG levels included body weight, lean body mass weight, BMI and age, for HDL-c levels included BMI, CD3 + CD4 + count and body weight, and for LDL-c levels included BMI and follow-up duration (Table 3).
Table 2
Spearman correlation analysis between lipid metabolism parameters and age, anthropometric parameters, and immunological and virological indicators (n = 61)
Variable
|
TC (mmol/L)
|
TG (mmol/L)
|
HDL-c (mmol/L)
|
LDL-c (mmol/L)
|
UA (µmol/L)
|
r
|
p
|
r
|
p
|
r
|
p
|
r
|
p
|
r
|
p
|
NAFLD(1 = without,2 = with)
|
0.357
|
0.002
|
0.353
|
0.003
|
-0.255
|
0.033
|
0.251
|
0.038
|
0.320
|
< 0.0001
|
Age (yr.)
|
0.304
|
< 0.0001
|
0.164
|
0.004
|
|
|
0.226
|
< 0.0001
|
-0.151
|
< 0.0001
|
Body weight (kg)
|
0.243
|
0.013
|
0.241
|
0.014
|
-0.413
|
< 0.0001
|
0.341
|
< 0.0001
|
0.338
|
< 0.0001
|
Body mass index (kg/m2)
|
0.343
|
0.001
|
0.236
|
0.021
|
|
|
0.418
|
< 0.0001
|
|
|
Body fat percentage (%)
|
0.318
|
0.002
|
0.460
|
< 0.0001
|
-0.238
|
0.020
|
0.283
|
0.006
|
|
|
Body fat weight (kg)
|
0.312
|
0.002
|
0.390
|
< 0.0001
|
-0.338
|
0.001
|
0.326
|
0.001
|
|
|
Body nonfat weight (kg)
|
|
|
|
|
-0.378
|
< 0.0001
|
0.319
|
0.002
|
0.377
|
< 0.0001
|
CD3 + CD4 + count (cells/µl)
|
|
|
|
|
|
|
|
|
0.161
|
< 0.0001
|
Virus load (IU/ml)
|
|
|
|
|
|
|
|
|
0.306
|
0.001
|
Follow-up duration
|
0.192
|
< 0.0001
|
|
|
0.281
|
< 0.0001
|
|
|
|
|
Abbreviations: NAFLD, nonalcoholic fatty liver disease. TG, triglyceride. TC, total cholesterol. LDL-c, low-density lipoprotein cholesterol. HDL-c, high-density lipoprotein cholesterol. UA, uric acid. |
Table 3
Multiple stepwise regression analysis of influencing factors, including age, anthropometric parameters, immunological and virological indicators on lipid and uric metabolism parameters (n = 61)
Independent variable
|
|
B
|
Std. Error
|
Beta
|
t
|
p
|
TC (mmol/L)
|
constant
|
3.224
|
0.681
|
-
|
4.733
|
< 0.0001
|
Body weight (kg)
|
0.053
|
0.017
|
0.781
|
3.161
|
0.002
|
Age (yr.)
|
0.031
|
0.007
|
0.369
|
4.249
|
< 0.0001
|
Body nonfat weight (kg)
|
-0.064
|
0.028
|
-0.578
|
-2.319
|
0.023
|
Follow-up weeks
|
0.006
|
0.002
|
0.269
|
3.308
|
0.003
|
TG (mmol/L)
|
constant
|
18.767
|
5.130
|
-
|
3.658
|
0.001
|
Body weight (kg)
|
0.902
|
0.192
|
3.564
|
4.696
|
< 0.0001
|
Body nonfat weight (kg)
|
-0.768
|
0.157
|
-1.883
|
-4.889
|
< 0.0001
|
Body mass index (kg/m2)
|
-1.684
|
0.477
|
-1.798
|
-3.528
|
0.001
|
Age (yr.)
|
0.095
|
0.042
|
0.293
|
2.249
|
0.031
|
HDL-c (mmol/L)
|
constant
|
1.153
|
0.169
|
-
|
6.805
|
< 0.0001
|
Body mass index (kg/m2)
|
0.070
|
0.015
|
0.791
|
4.699
|
< 0.0001
|
CD3 + CD4 + count (cells/ul)
|
0.001
|
0.000
|
0.423
|
4.930
|
< 0.0001
|
Body weight (kg)
|
-0.028
|
0.004
|
-1.145
|
-6.174
|
< 0.0001
|
LDL-c (mmol/L)
|
constant
|
1.056
|
0.374
|
-
|
2.827
|
0.006
|
Body mass index (kg/m2)
|
0.073
|
0.017
|
0.396
|
4.222
|
< 0.0001
|
Follow-up weeks
|
0.003
|
0.002
|
0.173
|
1.847
|
0.068
|
UA (µmol/L)
|
constant
|
323.772
|
15.315
|
-
|
21.141
|
< 0.0001
|
Virus load (IU/ml)
|
0.000
|
0.000
|
0.313
|
2.032
|
0.049
|
Abbreviations: TG, triglyceride. TC, total cholesterol. LDL-c, low-density lipoprotein cholesterol. HDL-c, high-density lipoprotein cholesterol. UA, uric acid. |
In addition, nonalcoholic fatty liver disease, body weight, lean body mass weight, CD3 + CD4 + cell count and virus load were all positively correlated with UA levels, while age was negatively correlated with UA levels (Table 2). Based on multiple stepwise regression analysis, only virus load was a risk factor for UA (Table 3).