Resumen

Los objetivos principales de este estudio son: demostrar la seguridad y eficacia de TPV/r en la población con VIH+ coinfectada con el virus de la hepatitis C (HCV) o el virus de la hepatitis B (HBV), con experiencia en tres clases de antirretrovirales (NRTI, NNRTI y PI) y con resistencia documentada a más de un PI. Determinar los datos farmacocinéticos en esta población coinfectada y la utilidad potencial del monitoreo terapéutico de fármacos (TDM) para mejorar los resultados de eficacia.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

HIV-1 infected males or females at least 18 years of age.
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.
CD4+ T lymphocyte count ≥50 cells/µl and HIV-1 VL ≥1000 copies/mL at screening.
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).
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.
Acceptable screening laboratory values that indicate adequate baseline organ function.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< Division of AIDS (DAIDS) Grade 3.
Acceptable medical history, as assessed by the investigator.
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.
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.
Karnofsky performance score ≥70.
Use of concomitant drugs that may significantly reduce plasma levels of the study medications.
Use of immunomodulatory drugs or antineoplastic agents within 30 days before study entry or during the trial.
Inability to adhere to the requirements of the protocol, including active substance abuse, as defined by the investigator.
Anticipated need for an interferon-based regimen in the 48 weeks following the study entry.
Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis.
Any active infection or neoplasm currently being treated.
Patients with history of hemorrhagic stroke or intracranial aneurysm.
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.
Patients with current history of alcohol abuse defined as alcohol consumption that would interfere with patient's compliance or result in biological abnormalities.

Criterios de exclusión

Prior tipranavir use.
Known hypersensitivity to any of the ingredients to the tipranavir or ritonavir formulations.
ARV medication naive.
Genotypic resistance to Tipranavir (TPV) (defined as a TPV mutation score of more than 7).
Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the month prior to screening.
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.
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.

Seguridad y actividad antiviral de TPV en pacientes con VIH coinfectados con hepatitis C o hepatitis B: evaluación piloto aleatorizada con monitoreo terapéutico de fármacos (TDM)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

tipranavir

ritonavir

Ubicaciones

1182.99.54001

Patrocinadores