Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum...

3
Study Design UIHC HIV Clinic Patients Invitation – Informed Consent eparinized Blood/Serum Obtained CD4, HIV VL measured Serum => GBV-C VL Cells => flow cytometry s GBV-C alter B cell & NK cell activat r alter monocyte CCR5/CXCR4 expression C blunts T cell activation & prolifera C induces chemokines C CCR5 and CXCR4 on CD4 cells C replicates in T and B cells C D 4 C ounts ART G B- ART G + H + G B- H + G B+ 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 C D 4 count P=0.01 N=11 N=13 N=11 N=9 HIV VL G B - G B + 0 100000 200000 300000 400000 500000 600000 H IV VL ns

Transcript of Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum...

Page 1: Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum Obtained CD4, HIV VL measured Serum => GBV-C VL Cells => flow.

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

Page 2: Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum Obtained CD4, HIV VL measured Serum => GBV-C VL Cells => flow.

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

Page 3: Study Design UIHC HIV Clinic Patients Invitation – Informed Consent Heparinized Blood/Serum Obtained CD4, HIV VL measured Serum => GBV-C VL Cells => flow.

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.