Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum...
-
Upload
raymond-bennett -
Category
Documents
-
view
213 -
download
0
Transcript of Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum...
Study Design
UIHC HIV Clinic PatientsInvitation – Informed Consent
Heparinized Blood/Serum Obtained
CD4, HIV VL measuredSerum => GBV-C VL
Cells => flow cytometry
Does GBV-C alter B cell & NK cell activationor alter monocyte CCR5/CXCR4 expression?
GBV-C blunts T cell activation & proliferationGBV-C induces chemokinesGBV-C CCR5 and CXCR4 on CD4 cellsGBV-C replicates in T and B cells
CD4 Counts
ART GB- ART G+ H+ GB- H+ GB+0
100200300400500600700800900
1000110012001300
CD
4 c
ou
nt
P=0.01
N=11 N=13 N=11 N=9
HIV VL
GB - GB +0
100000
200000
300000
400000
500000
600000H
IV V
Lns
CD19+ CD86+
ART GB- ART G+ H+ GB- H+ GB+0.0
2.5
5.0
7.5
10.0%
of
Cel
lsP=0.018
CD56brt CD16- / CD69+
ART GB- ART G+ H+ GB- H+ GB+0
5
10
15
20
25
% C
ell
s
P=0.009
B cell activation: GB+ < GB- p=0.024 HIV Viremic GB+ < GB- p=0.018
NK cell activation: CD56dim/CD16+: NS CD56brt/CD16-: If HIV RNA neg: NS If HIV RNA pos: GB+ < GB- p=0.009
CD14+/CCR5+
ART GB- ART G+ H+ GB- H+ GB+0
5
10
15
20
25
30
35
40
45
% C
ell
sMonocyte CCR5 expression GB+ < GB- p=0.009 HIV RNA+: GB+ < GB- p=0.03
CXCR4 GB+< GB-, but NS
CD14+/CXCR4+
ART GB- ART G+ H+ GB- H+ GB+40
50
60
70
80
90
100
% C
ell
s
P=0.03
Conclusion:GBV-C replication in vivo• Diminishes B cell activation• Blunts CD16+ NK cell activation• Downregulates monocyte CCR5
GBV-C replicates in T and B cells; however, replication limited to a very small percentage of cells.
Replication has not been shown in NK cells or monocytes. Effect in these cells may be due to induction of chemokines and/or cytokines
The effect of GBV-C activation on T and B lymphocytes, NK cells and monocytes may contribute to prolonged survival in HIV- infected individuals.