Summary of population
2,883 records of individuals initiating second-line ART in center China during 2009-2014 were eligible for inclusion in this analysis, 1513(52.5%) were female and 1370 (47.5%) were male, the mean age was 48.0±8.2 years. 2867 (99.4%) were Han and 2791 (96.8%) were farmer. The comparison of Scio-Demographic characteristics of the patients at initiation of study is shown in Table 1.
Table 1 Scio-Demographic characteristics of AIDS patients at initiation of second-line cART
|
Variables
|
Total N=2883
|
Censored N=2700
|
Death N=183
|
Gender
|
|
|
|
Female
|
1513(52.5%)
|
1430(53.0%)
|
83(45.4%)
|
Male
|
1370(47.5%)
|
1270(47.0%)
|
100(54.6%)
|
Age (year)
|
|
|
|
18-40
|
471 (16.3%)
|
457 (16.9%)
|
14 (7.7%)
|
40-50
|
1358 (47.1%)
|
1291 (47.8%)
|
67 (36.6%)
|
50-65
|
1054 (36.6%)
|
952 (35.3%)
|
102 (55.7%)
|
Marital Status
|
|
|
|
Married
|
2405 (83.4%)
|
2254 (83.5%)
|
151 (82.5%)
|
Sig/window
|
478 (16.6%)
|
446 (16.5%)
|
32 (17.5%)
|
Race
|
|
|
|
Han
|
2867 (99.4%)
|
2685 (99.4%)
|
182 (99.5%)
|
Others
|
16 (0.55%)
|
15 (0.56%)
|
1 (0.55%)
|
Occupational status
|
|
|
|
Farmer
|
2791 (96.8%)
|
2613 (96.8%)
|
178 (97.3%)
|
Others
|
92 (3.19%)
|
87 (3.22%)
|
5 (2.73%)
|
Educational Status
|
|
|
|
≤6years
|
769 (26.7%)
|
719 (26.6%)
|
50 (27.3%)
|
>6years
|
2114 (73.3%)
|
1981 (73.4%)
|
133 (72.7%)
|
Among the patients in this study, a large proportion (81.1%) of the participants were infected HIV through plasma donate, 2637 (91.4%) and 2276 (78.9%) were more than 3 years been HIV positive and taken cART before second-line cART initiation. The median CD4 count was 312 (IQR:288) cells/μl. The comparison of treatment-related, clinical characteristics of AIDS patients at initiation of second-line cART is shown in Table 2.
Table 2 Treatment-Related, clinical characteristics of AIDS patients at initiation of second-line cART
|
Variables
|
Total N=2883
|
Censored N=2700
|
Death N=183
|
HIV transmission mode
|
|
|
|
Others
|
545 (18.9%)
|
515 (19.1%)
|
30 (16.4%)
|
Plasma
|
2338 (81.1%)
|
2185 (80.9%)
|
153 (83.6%)
|
Time on HIV Positive (year)
|
|
|
|
<3
|
246 (8.53%)
|
235 (8.70%)
|
11 (6.01%)
|
3-8
|
1532 (53.1%)
|
1425 (52.8%)
|
107 (58.5%)
|
>8
|
1105 (38.3%)
|
1040 (38.5%)
|
65 (35.5%)
|
Time on cART before Second-line (year)
|
|
<3
|
607 (21.1%)
|
573 (21.2%)
|
34 (18.6%)
|
3-8
|
1687 (58.5%)
|
1565 (58.0%)
|
122 (66.7%)
|
>8
|
589 (20.4%)
|
562 (20.8%)
|
27 (14.8%)
|
Chinese Medicine Therapy
|
|
|
|
no
|
2064 (71.6%)
|
1915 (70.9%)
|
149 (81.4%)
|
yes
|
819 (28.4%)
|
785 (29.1%)
|
34 (18.6%)
|
Calendar year of Second-line cART Initiation
|
|
2009
|
70 (2.40%)
|
60 (2.2%)
|
10(5.5%)
|
2010
|
457 (15.9%)
|
422 (15.6%)
|
35 (19.1%)
|
2011
|
325 (11.3%)
|
298 (11.0%)
|
27 (14.8%)
|
2012
|
704 (24.4%)
|
660 (24.4%)
|
44 (24.0%)
|
2013
|
666 (23.1%)
|
637 (23.6%)
|
29 (15.8%)
|
2014
|
661 (22.9%)
|
623 (23.1%)
|
38 (20.9%)
|
CD4 Cell Count (cells/ μl)
|
|
|
200-
|
820 (28.4%)
|
732 (27.1%)
|
88 (48.1%)
|
200-350
|
812 (28.2%)
|
772 (28.6%)
|
40 (21.9%)
|
350-500
|
622 (21.6%)
|
593 (22.0%)
|
29 (15.8%)
|
500+
|
629 (21.8%)
|
603 (22.3%)
|
26 (14.2%)
|
Hemoglobin ()
|
|
|
|
>110
|
2401 (83.1%)
|
2247 (83.2%)
|
154 (84.2%)
|
≤110
|
482 (16.9%)
|
453 (16.8%)
|
29 (15.8%)
|
AST or ALT ()
|
|
|
|
<50
|
1617 (56.1%)
|
1529 (56.6%)
|
88 (48.1%)
|
≥50
|
1266 (43.9%)
|
1171 (43.4%)
|
95 (51.9%)
|
The mortality and associated factors of those population
Of the 2883 participants followed for 3 years including 8445 person-years, 183 (6.5%) died, 14(0.5%) lost follow-up and the mortality rate 2.17/100 person-years. 98.0% of patients were alive after 1 year, 95.9% after 2 years, 93.5% after 3 years of initiated this study.
The results of univariable Cox proportional hazards model analyzed factors associated with mortality of AIDS patients were showed in table 3. older than 50 years, CD4 littler than 200 cells/μl, AST or ALT higher than 50 were the risk factors of mortality. Treated with Chinese medicine could decrease the risk of mortality. Gender, marital status, education status, time on HIV positive, time on cART before second-line and hemoglobin were not the effected variable of mortality.
Gender, age, Chinese medicine therapy, CD4 cell count and AST or ALT were selected for multivariable Cox proportional hazards model. Age older than 50 years (HR,3.37; 95%CI, 1.92-5.92), Chinese medicine therapy (HR,0.48; 95%CI, 0.33-0.71), CD4 littler than 200 cells/μl (HR,2.97; 95%CI, 1.90-4.64), AST or ALT higher than 50 (HR,1.55; 95%CI, 1.15-2.11) were each independently associated with mortality. The results showed in table 3.
Analysis the risk group
After the multivariable analysis, age, CD4 cell count, Chinese medicine therapy and unmoral AST/ALT were the explanatory variables on time to death after initiation of second-line cART. The group of age<50 years followed for 3 years including 5395 person-years, 81 (5.5%) died, and the mortality rate 1.50/100 person-years. The group of age >50 years followed for 3 years including 3050 person-years, 102(10.0%) died, and the mortality rate 3.34/100 person-years (fig 1 A).The group of cd4>200 followed for 3 years including 6099 person-years, 95 (4.7%) died, and the mortality rate 1.56/100 person-years. The group of CD4 <200 years followed for 3 years including 2346 person-years, 88 (11.0%) died, and the mortality rate 3.75/100 person-years (fig 1 B).No Chinese therapy group followed for 3 years including 6024 person-years, 149 (7.4%) died, and the mortality rate 2.47/100 person-years. Chinese therapy group followed for 3 years including 2421 person-years, 34 (4.2%) died, and the mortality rate 1.40/100 person-years (fig 1 C). The group of AST or ALT <50 followed for 3 years including 4753.5 person-years, 88 (5.7%) died, and the mortality rate 1.85/100 person-years. The group of AST or ALT >50 followed for 3 years including 3691.5 person-years, 95 (7.6%) died, and the mortality rate 2.57/100 person-years (fig 1 D).
Table 3 Cox proportional Hazards Model Showing the Association of variables
|
Variables
|
3 years mortality(%)
|
Univariable
|
Multivariable
|
HR(95% CI)
|
P value
|
HR(95% CI)
|
P value
|
Gender
|
|
|
|
|
|
Female
|
5.49
|
1[Reference]
|
NA
|
1[Reference]
|
NA
|
Male
|
7.30
|
1.30(0.97, 1.74)
|
0.079
|
1.25(0.93,1.68)
|
0.136
|
Age(year)
|
|
|
|
|
|
18-40
|
2.97
|
1[Reference]
|
NA
|
1[Reference]
|
NA
|
40-50
|
4.93
|
1.67(0.94,2.97)
|
0.081
|
1.73(0.97,3.09)
|
0.062
|
50-65
|
9.68
|
3.24(1.85,5.67)
|
<0.001
|
3.37(1.92,5.92)
|
<0.001
|
Chinese Medicine Therapy
|
|
|
no
|
7.22
|
1[Reference]
|
NA
|
1[Reference]
|
NA
|
yes
|
4.15
|
0.58(0.40,0.84)
|
0.004
|
0.48(0.33,0.71)
|
<0.001
|
CD4 Cell Count (cells/μl)
|
|
|
500+
|
4.13
|
1[Reference]
|
NA
|
1[Reference]
|
NA
|
350-500
|
4.66
|
1.21(0.71,2.07)
|
0.488
|
1.25(0.73,2.14)
|
0.413
|
200-350
|
4.92
|
1.27(0.77,2.09)
|
0.357
|
1.35(0.81,2.22)
|
0.247
|
200-
|
10.73
|
2.84(1.82,4.43)
|
<0.001
|
2.97(1.91,4.64)
|
<0.001
|
AST or ALT (u/L)
|
|
|
|
<50
|
5.44
|
1[Reference]
|
NA
|
1[Reference]
|
NA
|
≥50
|
7.50
|
1.39(1.04,1.86)
|
0.027
|
1.55(1.15,2.11)
|
0.005
|
Factors Not Selected
|
Marital Status
|
|
|
|
|
|
Sig/window
|
6.69
|
1[Reference]
|
NA
|
NA
|
NA
|
Married
|
6.27
|
0.95(0.65,139)
|
0.778
|
NA
|
NA
|
Educational Status
|
|
|
|
≤6years
|
6.50
|
1[Reference]
|
NA
|
NA
|
NA
|
>6years
|
6.29
|
0.97(0.70,1.34)
|
0.854
|
NA
|
NA
|
Time on HIV positive (year)
|
|
|
|
<3
|
4.47
|
1[Reference]
|
NA
|
NA
|
NA
|
3-8
|
6.98
|
1.52(0.82,2.83)
|
0.187
|
NA
|
NA
|
>8
|
5.88
|
1.28(0.68,2.43)
|
0.450
|
NA
|
NA
|
Time on cART before Second-line (year)
|
|
|
|
<3
|
5.60
|
1[Reference]
|
NA
|
NA
|
NA
|
3-8
|
7.23
|
1.26(0.86,1.84)
|
0.235
|
NA
|
NA
|
>8
|
4.58
|
0.78(0.47,1.29)
|
0.334
|
NA
|
NA
|
Hemoglobin ( )
|
|
|
|
>110
|
6.41
|
1[Reference]
|
NA
|
NA
|
NA
|
≤110
|
6.02
|
0.96(0.65,1.43)
|
0.844
|
NA
|
NA
|
|