Leukapheresis for Research on HCV-Coinfected Patients

Hepatitis C virus (HCV) and Hepatitis B (HBV) infection are known to cause morbidity and
mortality especially among those who are coinfected with Human Immunodeficiency virus (HIV).
HCV infected individuals who are also coinfected with HIV have more rapid progression of
liver disease, abnormal diagnostic serologies, higher levels of HCV viremia, and markedly
lower levels of therapeutic responses to the standard combination therapy with peginterferon
and ribavirin.

The underlying immunopathogenesis of HCV and HBV infection, progression of liver disease, and
interactions with HIV are not yet clearly understood. A clear understanding of the immune
correlates of protection against HCV and HBV are important in development of a vaccine for
HCV and novel immune-based therapeutics for the cure of HBV.

This study will recruit individuals who are coinfected with HIV and HCV and/or HBV as well as
those who are monoinfected with HCV or HBV. The study will enroll 2 groups. Participants in
the first group (hereafter referred to as Group 1) will consist of participants recruited for
research and clinical related blood draws, leukapheresis, and liver biopsies for long term
study participation. Participants in the second group (hereafter referred to as Group 2) will
consist of participants with known or suspected HCV and/or HBV who need assistance with
diagnosis or treatment.

Participants in Group 1 will be apheresed or undergo blood draw several times after
enrollment and may be followed for up to 10 years. Participants in Group 2 will be evaluated
for HBV and/or HCV infection or complications, or receive treatment. The expectation is that
may be followed for one year.

Leukapheresis is used in Group 1 in order to obtain sufficient cells to pursue the following
objectives: delineating B cell response to CD4+ T cell help, delineating CD8+ T factors
associated with suppression of viral replication and normalization of immune function,
characterizing natural killer function relative to HCV and/or HBV disease, and identifying
biomarkers for progression of liver disease. The required number of mononuclear cells needed
to perform these experiments can be easily and safely obtained using leukapheresis procedures
in the Clinical Center Apheresis Unit. Participants who do not meet apheresis criteria may
participate through routine blood draws to contribute to this research. All participants in
Group 1 may also receive a liver biopsy at NIH (every 3 years for HIV/HCV coinfected and all
HBV infected and every 5 years for HCV monoinfected subjects) to assess the progression of
liver disease.

Treatment plans for Group 2 HBV and/or HCV will be in accordance with standard medical
practice, and the number and length of additional visits and diagnostic evaluations will vary
accordingly.

- INCLUSION CRITERIA FOR BOTH GROUPS:

- Adult (18 years old or older)

- Either monoinfected with HCV or coinfected with HCV and HIV

- Willingness to give informed consent.

- Willing to undergo genetic testing

- Willing to have samples stored for future research.

- Must have a referring physician or clinic that will continue to provide medical care.

Note: An HCV/HIV coinfected individual is defined as any individual with all the following:
1) Positive ELISA and western blot test for HIV, and 2) Positive serology and/or positive
HCV RNA test; An HCV monoinfected individual is defined as any individual with all of the
following: 1) Positive serology and/or positive HCV RNA test, and 2) Negative ELISA test
for HIV

INCLUSION CRITERIA FOR GROUP 1:

-Must be willing and able to make follow up visits for leukapheresis and blood draws at
least once in the next 6 months

INCLUSION CRITERIA FOR GROUP 2:

-Must be referred by a physician for the purposes of confirming HCV diagnosis,
complications from HCV, or standard HCV treatment management.

EXCLUSION CRITERIA FOR BOTH GROUPS

Have any other condition, which the investigator considers a contraindication to study
participation.

EXCLUSION FOR GROUP 1:

- Evidence of liver failure on liver biopsy, abdominal ultrasound, or liver function
blood tests

- Receiving HCV therapy at the time of enrollment

- Platelet count < 50,00 per mL

- Hematocrit < 28 percent.