Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant

RETROSPECTIVE ARM INCLUSION CRITERIA

The intent of the Retrospective Arm is to capture all HIV/HCV coinfected patients exposed to sofosbuvir based DAA therapy since 2014, to mirror the population enrolled in the Prospective Arm.

Liver transplant candidates (listed) and decompensated cirrhotics (not listed) for liver transplant

• Treated with sofosbuvir based DAA for any duration since 2014
• Age >18 years at time of treatment
• Pre-treatment Child's Pugh score of 7 or greater
• Pre-treatment laboratory MELD >=6 and = 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
• HCV genotype 1, 4, 5 or 6

Liver transplant recipients

• Treated with sofosbuvir based DAA post liver transplant for any duration since 2014
• Liver transplant from 2000 to current
• Age >18 years at time of treatment
• Treated initiated at least 1 month post-liver transplant
• Post-LT stage of liver disease documented within the prior year of treatment start date by standard of care methods of liver staging
• Survived at least 12 weeks after start of treatment
• HIV-positive on stable ART for at least 4 weeks pre-treatment
• Chronic HCV infection with at least one measurement of plasma HCV RNA >= 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
• Fibrosis staging done within 1 year of start of DAA therapy
• HCV genotype 1, 4, 5 or 6

PROSPECTIVE ARM INCLUSION/EXCLUSION CRITERIA

Pre-liver transplant candidates

• Enrollment will be targeted to occur at least 12 weeks prior to anticipated transplant date.
• Screening laboratory MELD >=6 and =6 and 12 weeks

Inclusion Criteria

• Over 18 years of age at screening
• Female participants of child bearing potential must have a negative urine pregnancy test at day 0 prior to dosing.
• Has received a liver transplant for HCV or has decompensated cirrhosis (Child's Pugh score of 7 or greater)
• Have HIV-1 infection and either:
• On HIV medications (antiretrovirals) for at least 4 weeks WITH
• An HIV viral load less than the level of detection OR
• On no HIV medications for at least 8 weeks WITH:
• A CD4 count of 500 cells/mm3 or more OR
• HIV viral load of = 1, 000 IU/mL during screening and at least one of the following:

A positive anti-HCV antibody, HCV RNA, or an HCV genotype test at least 12 months prior to baseline (Day 0) visit together with positive HCV RNA test

• HCV genotype 1, 4, 5 or 6
• The use of an anti-HCV positive donor is allowed for participants who have detectable HCV RNA at the time of transplant.
• The use of an HIV+ donor is allowed if the participant is enrolled in an IRB approved HOPE Act protocol at the transplant site. If the HIV+ donor is also HCV co-infected, then the recipient must have detectable HCV RNA at the time of transplant.
• Able to effectively communicate with the Investigator and other center personnel.
• Willing to give written informed consent and comply with the study restrictions and requirements.
• Willingness to allow stored blood or tissue samples to be used in the future for studying liver disease and immune function.
• Willingness to permit HLA typing to be performed.
• Have a transplant team available for all primary and transplant-related care.
• If not yet transplanted: expected to be at least 12 weeks prior to transplant in order to complete treatment course.
• If not yet transplanted: Must have prior standard of care liver staging consistent with F4.
• If not yet transplanted: For pre-LT patients with HCC, they must meet Milan criteria at time of enrollment to be eligible
• If post-liver transplant, must be at least 1 month since transplant procedure to begin treatment.
• If post-liver transplant, liver disease staging must be documented within the prior year by standard of care methods of liver staging

Exclusion Criteria

• Positive HBsAg at screening.
• History of any other clinically active chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson's disease, >=1 an