GBVC infection is associated with less T cell activation in recently HIV1infected subjects and is in

1

• GBV-C infection is associated with less T cell
  activation in recently HIV-1-infected subjects
  and is independent of HIV-1 viral load.
• Maidana Giret M.T.1, Silva T.M.1, Levi J.E.2,
  Bassichetto K.C.3, Nishiya A.4, Sabino E.4,
  Palácios R.1, Kallás E.G.1
• 1 Federal University of São Paulo, Medicine, São
  Paulo, Brazil, 2 Institute of Tropical Diseases
  of São Paulo, São Paulo, Brazil, 3 Public Health
  Department of São Paulo, São Paulo, Brazil, 4
  Blood Center of São Paulo, São Paulo, Brazil
• July 23, 2007

2
GBV-C

• ssRNA, 9400 nucleotides, Flaviviridae virus,
  described in 1995
• Replicates in several immune cells, including
  lymphocytes and dendritic cells
• Transmission parenteral, sexual, IVDU
• Plasma viremia and anti-E2 envelope glicoprotein
  antibodies are mutually exclusive

3
Methods

• Establishment of an testing and counseling sites
  and laboratories network
• STARHS 170 days
• Prospective enrollment into the cohort recently
  HIV-1infected subjects

STARHS
170 days
1.2
Threshold for
Threshold for
Less
-
sensitive EIA
Less
-
sensitive EIA
1

-
0.8
0.6
HIV antibody concentration
0.4


0.2
Threshold for sensitive EIA
Threshold for sensitive EIA
0
1
2
3
4
5
6
7
8
9
10
11
12
Months
4
Methods

• GBV-C RNA status nested PCR
• GBV-C RNA viral load real-time PCR
• GBV-C antibody (anti-E2) ELISA
• HIV-1 viral load and T cell counts
• Expanded immunophenotyping by Flow Cytometry
• Genotyping for CCR5D32

344 bp
5

Methods
CD8 T cells
CD4 T cells
58.7
21.9
21.4
17.8
5
5
10
10
4
4
10
10
CD38
3
3
10
10
2
2
10
10
0
0
10.7
8.73
9.61
51.2
2
3
4
5
2
3
4
5
0
10
10
10
10
0
10
10
10
10

CCR5
6
Results

• Viremia GBV-C 26 Anti-E2 24
• 49 randomly selected subjects
• 89.1 Men Median age 33 (IQR 25.1 - 33.3)
• Median CD4 T cell count 507 cells/ml (IQR 431
  - 602)
• Median viral load 16,900 HIV-RNA copies/mL (IQR
  3,615 - 48,700)

7
CD38 and CCR5 expression
CCR5
GBV-C-
GBV-C
GBV-C-
GBV-C
8
Correlation between Viral Load and CD38CD8 T
cells
p lt 0.005 r 0.41
p 0.45 r - 0.16
9
Importance of GBV-C status on CD38CD8 and HIV-1
Viral Load
10
Multivariate regression model
Dependent variables
Coefficient and p values. NS not significant
11
GBV-C -
CD4
CD4
GBV-C
CD3
CD69
CD25
12
Others activation markers
CD69
HLA-DR
CD25
ns
plt0,0001
plt0,01
plt0,05
ns
plt0,05
13
Conclusions

• A considerable frequency of GBV-C co-infection is
  observed in HIV-1 infected individuals (viremia
  in 26, abs in 24).
• GBV-C active infection is associated with less
  CD4 and CD8 T cell activation, measured by
  different cellular surface markers.
• This association is independent of lymphocyte
  counts, HIV viral load, and CCR5D32 polymorphism.

14
Perspective

• This effect may be one of the key mechanisms
  involved in the protection conferred by GBV-C to
  HIV-1-infected subjects.
• It might lead to new therapeutic approaches for
  HIV infection.

15
Acknowledgements
Federal University of São Paulo Esper Georges
Kallas Institute of Tropical Medicine of São
Paulo Luis Eduardo Levi Public Health Department
of São Paulo Kátia Bassichetto Blood Center of
São Paulo Prof. Dr. Ester Sabino Dietmar Zdunek
Roche Diagnostics