Brain Deficits in HIV/HCV Coinfected People Before and After Anti-HCV Therapy

The World Health Organization estimates at least 3% of the world's population is infected
with chronic hepatitis C virus (HCV), and up to one third of all HIV infected people are
coinfected with HCV. HCV can damage the liver cells and cause liver diseases such as
cirrhosis and hepatocellular carcinoma. People infected with HCV can also suffer from
neurocognitive deficits, including problems with information processing, slowing of muscular
processes related to thinking, and difficulty focusing on complex things. These
neurocognitive deficits are similar to those found in HIV infected individuals, and previous
research indicates that people infected with both HIV and HCV have greater overall cognitive
impairments. This study aims to determine the impact of anti-HCV treatment on
neurocognitive, neuropsychiatric, and neuroimaging factors in people infected with HCV and
people coinfected with both HCV and HIV. The study also aims to measure whether possible
neurocognitive improvements from anti-HCV treatment are related to a physical health
outcome, measured as a sustained virologic response, and whether adherence to the medication
schedule laid out for the participants influences possible positive effects on either
neurocognitive or physical health.

Two kinds of participants will be recruited for this study: those infected with HCV and
those infected with both HCV and HIV. These two groups will be compared to determine how
comorbid HCV and HIV infection affects treatment outcomes. The treatment specified for HCV
is pegylated interferon alfa and ribavirin (PEG-IFN/RBV), considered standard care for
patients with chronic HCV. Participants will continue to see their doctors as regularly
scheduled, and any other prescribed medications or advice concerning HCV treatment will be
noted by researchers. All participants will be tested at baseline, after 12 weeks of
treatment, and 12 weeks after the completion of treatment. A subset from each group of
participants will undergo additional neuroimaging tests. Participation in this study will
last for varied amounts of time depending on the recommended treatments for HCV. Based on
each virus' genotype and rapid virologic response, the treatment period for HCV may last 24
or 48 weeks, with further extensions of 12 to 24 weeks in some cases.

During the three testing sessions, each lasting 5 hours, participants' health, cognitive
functioning, and medication adherence will be measured. Testing will include self-report
measures, intelligence tests, tasks designed to assess cognitive functioning, and motor
functioning tasks. Urine tests screening for narcotics will also be collected. In addition
to self-report measures, caps to pill bottles storing HCV medication will automatically
record every time the cap is removed to measure adherence to the medication schedule.

Inclusion Criteria:

- Diagnosis of HCV with detectable HCV RNA in serum

- Meets clinical criteria for initiating HCV therapy

- Lives in the community and not in a board and care, nursing home, hospice, or other
residential setting in which a professional caregiver would dispense necessary
medication. Living with a partner, roommate, or other family members who may assist
with caregiving, including reminding participants to take medication, is acceptable.

- Responsible for administering own medications

- Diagnosis of HIV-associated neurocognitive disorder (HAND) will not be cause for
exclusion, so long as participant is able to demonstrate the ability to grant full
informed consent

- HIV or HCV disease severity will not be cause for exclusion (e.g., CDC Groups A, B,
and C are all eligible); although, if severely ill because of either HIV (e.g.,
uncontrolled viremia, severely immunosuppressed) or HCV (e.g., cryoglobulinemia,
hepatic encephalopathy) will not be eligible for PEG-IFN/RBV therapy

- Able to read English at the 6th grade level

Exclusion Criteria:

- Current or past psychotic spectrum disorder, including schizophrenia,
schizophreniform disorder, or bipolar disorder

- History of learning disability, seizure disorder, closed-head injury with loss of
consciousness in excess of 30 minutes, or any other neurological disease

- Evidence of any central nervous system opportunistic infection or neoplasm

- Diagnosed with Hepatitis B

- Previous failed course of HCV therapy

- Those judged to be significantly depressed by the study psychiatrists/psychologists
(defined as current major depressive disorder of moderate or severe severity) or with
evidence of suicidal ideation will not be enrolled until clinical condition is
stabilized.