Safety and Antiviral Activity of TPV in HCV and/or HBV HIV Coinfected Patients TDM Randomised Pilot Evaluation
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: tipranavir; ritonavir
Intervention MeSH terms: Ritonavir; Tipranavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: treatment experienced

Summary:

      The main purposes of this study are: demonstrate the safety and efficacy of TPV/r among HCV
      or hepatitis B virus (HBV) co-infected HIV+population, three-class (NRTI, NNRTI, and PI)
      experienced, with documented resistance to more than one PI. Determine pharmacokinetic data
      in this co-infected population and potential utility of using therapeutic drug monitoring
      (TDM) in improving efficacy outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV-1 infected males or females at least 18 years of age.

          2. Three-class (Nucleoside reverse transcriptase inhibitor (NRTI), Non nucleoside reverse
             transcriptase inhibitor (NNRTI), and Protease inhibitor (PI)) treatment-experienced (a
             minimum of 3-months duration for each class) with resistance to more than one PI (on
             the screening resistance testing). Patients that are NNRTI-naïve patients but who have
             genotypically documented NNRTI-resistance mutations on past or screening resistance
             testing would be eligible.

          3. CD4+ T lymphocyte count ≥50 cells/µl and HIV-1 VL ≥1000 copies/mL at screening.

          4. The ARV study treatment regimen must consist of new TPV/r in combination with an OBR
             of 2-4 agents of the following: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or,
             where available, an Expanded Access Program (EAP) investigational agent (Section 3.3).
             In total, patients are to have an ARV study treatment regimen consisting of at least 3
             agents (TPV/r and two OBRs).

          5. Chronic hepatitis C Virus (HCV) infection demonstrated by HCV-ribonucleic acid (RNA)
             positivity or, Chronic hepatitis B (HB) infection demonstrated by anti HBc IgG
             Antibody and HB Surface Antigen positivity.

          6. Acceptable screening laboratory values that indicate adequate baseline organ function.

          7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < Division of AIDS
             (DAIDS) Grade 3.

          8. Acceptable medical history, as assessed by the investigator.

          9. Any AIDS defining illness listed in the Appendix 10.3.1 should be accepted as long as
             is resolved, asymptomatic or stable on treatment for at least 12 weeks before
             screening (Visit 1); the AIDS defining events listed below are not acceptable History
             of Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS),
             and/or any malignancy.

         10. A reliable method of barrier contraception will be used by all female patients who are
             of reproductive potential, for at least three months prior to Visit 3, during the
             trial, and 30 days after completion or termination from the trial.

         11. Karnofsky performance score ≥70.

        Exclusion Criteria:

          1. Prior tipranavir use.

          2. Known hypersensitivity to any of the ingredients to the tipranavir or ritonavir
             formulations.

          3. ARV medication naive.

          4. Genotypic resistance to Tipranavir (TPV) (defined as a TPV mutation score of more than
             7).

          5. Patients on recent drug holiday, defined as off ARV medications for at least 7
             consecutive days within the month prior to screening.

          6. Decompensated liver disease, including presence or history of ascites, variceal
             bleeding, or hepatic encephalopathy or having ever been diagnosed as having hepatic
             insufficiency of Child Pugh class B or C.

          7. Female patients of childbearing potential who:

               -  have a positive serum pregnancy test at screening,

               -  are breast feeding,

               -  are planning to become pregnant,

               -  are not willing to use a barrier method of contraception, or

               -  are only willing to use an estrogen-containing medication, e.g., ethinyl
                  estradiol, as a method of contraception.

          8. Use of investigational medications within 30 days before study entry or during the
             trial except for those investigational ARV drugs permitted during the trial as stated
             in inclusion criteria 6.

          9. Use of concomitant drugs that may significantly reduce plasma levels of the study
             medications.

         10. Use of immunomodulatory drugs or antineoplastic agents within 30 days before study
             entry or during the trial.

         11. Inability to adhere to the requirements of the protocol, including active substance
             abuse, as defined by the investigator.

         12. Anticipated need for an interferon-based regimen in the 48 weeks following the study
             entry.

         13. Any other or additional plausible cause for chronic liver disease, including the
             presence of other viruses known or suspected to cause hepatitis.

         14. Any active infection or neoplasm currently being treated.

         15. Patients with history of hemorrhagic stroke or intracranial aneurysm.

         16. Patients with history of ischemic stroke, neurosurgery, skull trauma and/or
             intracranial pathology (arteriovenous malformation, brain tumors and cerebral venous
             thrombosis) within 4 weeks prior to screening (Visit 1) as assessed by investigator.

         17. Patients with current history of alcohol abuse defined as alcohol consumption that
             would interfere with patient's compliance or result in biological abnormalities.