The changes in plasma cytokines levels following HAART and their relationship with HIV VL before and after six months of HAART treatment were investigated. In the above context, the study performed and determined relationship between IL -2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, plasma levels and HIV VL at initiation and after six months of HAART for one hundred study participants and fifteen participants HIV naïve as controls. Our findings showed statistically significant differences in plasma cytokines levels at initiation and after six months of HAART. A positive correlation was found between IL-10, IL-6 with HIV VL and a negative correlation was found between IFN-γ, TNF- α and HIV VL.
Social demographic characteristics of participants
Among HIV positive clients, 50 clients were HAART naïve, while 50 clients were on HAART for at least 6 months. Based on sex, there were no statistically significance differences in male 24(48%) / 23(46%) and female 26(52%) /27(54%) at initiation and after 6 months of HAART respectively, Chi-square p-value 0.8411 (Table 1). The dominant groups of study participants (56% and 62%) were between 25 and 44 years old at initiation and after 6 months, respectively.
Table 1
Social demographic distribution of study participants
Parameters
|
Health
Group Control
N=15
|
HIV+HAART Naïve N=50 (%)
|
HIV+ HAART
after 6 months
N=50 (%)
|
p-value |
Sex
|
|
|
|
|
Males
|
7 |
24(48) |
23(46) |
0.8411 |
Females
|
8 |
26(52) |
27(54) |
|
Age
|
|
|
|
|
18–24
|
|
6(12) |
7(14) |
|
25–44
|
|
28(56) |
31(62) |
0.0032 |
45–64
|
|
16(32) |
12(24) |
|
Smoking
|
|
|
|
|
Yes
|
|
5(10)
|
1(2)
|
0.2123
|
No
|
|
45(90)
|
49(98)
|
|
Alcohol consumption
|
|
|
|
|
Yes
|
|
4(8)
|
2(4)
|
0.3997
|
No
|
|
46(92)
|
48(96)
|
|
Meals per day
|
|
|
|
|
One per day
|
|
5(10)
|
3(6)
|
0.0004
|
Two per day
|
|
43(86)
|
45(92)
|
|
Three per day
|
|
2(4)
|
2(4)
|
|
Eating fruits and vegetables
|
|
|
|
|
At least once week
|
|
35(70)
|
28(56)
|
|
Not all
|
|
15(30)
|
22(44)
|
0.147
|
Table 1: Number of participants: 50 participants at initial of HAART and 50 participants after 6 months on treatment. N = 100 (%) unless otherwise indicated; HIV: human immunodeficiency virus HAART: highly active antiretroviral treatment
Cytokines levels before and after initiation of HAART
This study found that the mean concentration and standard deviation of the mean (SD) in pg/ml for TNF-α, IFN-γ were increasing, 11.9(5.21) versus 35.3(16.2), 23.8 (10.4) versus 47.1(21.6), respectively. IL-2, IL-4, IL-6 and IL-10 were decreasing, 34.7 (9.43) versus 28(9.98), 10.7 (15.1) versus 7.72(6.19); 78.6(13.8) versus 54.8(17.0) and 45.7(15.1) versus 17.4(6.79), respectively following HAART (Fig. 1A, B, C, D, E and F).
In this study, we noticed a significant difference in plasma cytokines concentration following HAART as follows: IL-2 (t (98) = 3.3098 with a p-value = 0.0013), TNF-α (W = -9.770 with a p-value = 0.0001); IFN-γ (t (98) = -6.9009 with a p-value = 0.0001); IL-4 (W = 1721, p-value = 0.0118); IL-6 (t (98) = 5.78 with a p-value 0.0001); and IL-10 (W = 2413 with a p-value < 0.0001), (Fig. 2A, B).
The same difference was observed when compared with healthy controls, HAART naïve sub-population and a sub-population after six months of HAART.
Cytokines plasma levels did not show any statistically difference upon stratification based on age and sex at initiation and after six months with ANOVA. Although the data for this study revealed the high concentration and data overlap mostly for IL-2 and IL-6 in the strata of 25–44 years old (Fig. 2C and 2D).
Relationship between Cytokines and HIV VL
The linear relationship of IL-2, IL-4, IL-6, IL-10, and TNF-α and IFN-γ and HIV_VL were assessed using Pearson's Product Moment Coefficient (r). The positive relationship was observed for HIV_VL and IL-2 (r = 0.4148 p-value < 0.0001), HIV_VL and IL-6 (r = 0.8164 p-value < 0.0001), HIV_VL and IL-10 (r = 0.8667 p-value < 0.0001) while HIV_VL was associated negatively with TNF (r=-0.3483 p-value 0.0005) and IFN (r= -0.4835 p-value < 0.0001) (Table 2). IL-4 did not show statistically significant relationship with HIV VL (r = 0.0839 p-value = 0.41)
Table 2
The correlation analysis of cytokines with HIV viral load
|
Viral Load vs IL2
|
Viral Load
vs IFN-γ
|
Viral Load
vs TNF-α
|
Viral Load
vs IL4
|
Viral Load
vs IL6
|
Viral Load vs IL10
|
Pearson r
|
0.4148
|
-0.3483
|
-0.4835
|
0.08392
|
0.8164
|
0.8667
|
95% CI
|
0.2327
to 0.5688
|
-0.5138
to -0.1579
|
-0.6242
to -0.3124
|
-0.1196
to 0.2807
|
0.7359
to 0.8741
|
0.8059
to 0.9094
|
p-value
|
< 0.0001
|
0.0005
|
< 0.0001
|
0.4188
|
< 0.0001
|
< 0.0001
|
Table 2: The correlation analysis of pro inflammatory cytokine and anti inflamatory cytokine with HIV viral load.