Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Mar 28, 2001

Keywords

ClinConnect Summary

Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who have advanced liver disease (decompensated cirrhosis by Child-Pugh score and no known cause of hepatitis other than HBV), a HBV viral load of at least 1 million copies/mL blood, and at least one year of therapy with lamivudine will be treated with open-label adefovir dipivoxil 10 mg daily and lamivudine 150 mg bid to evaluate the safety and efficacy of this regimen in this patient group and to obtain specimens for studies of immune responses to HBV in HIV-infected patients. Additionally the kinetics...

Gender

ALL

Eligibility criteria

• INCLUSION CRITERIA:
• • Age greater than or equal to 18 years
• • Infection with HBV with HBV viral load greater than or equal to 1.0 x 10(6) copies/mL by Roche assay at screen
• • HIV-infected as documented by ELISA and Western Blot in NIAID clinic (any CD4/HIV viral load)
• • Decompensated cirrhosis (Child-Pugh Score greater than or equal to 7: Class B or C cirrhosis)
• • Class A with Score of 6 acceptable if secondary to ascites grading and not encephalopathy or laboratory abnormality (PT, albumin, bilirubin).
• • Able to return to NIH for study visits
• • Have a physician(s) outside of NIH who will provide routine, as well as HIV and liver specific, care.
• • Receiving lamivudine at a dose of at least 100 mg qd for greater than or equal to one year prior to enrollment (with no dosing interruptions of greater than 1 month total in the previous year and no interruption in the 3 months prior to study entry)
• • Serum creatinine less than 1.5 mg/dL
• • Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL)
• • Neutrophil count greater than or equal to 1000 cells/mm(3)
• • Platelets greater than or equal to 50,000/mm(3)
• • Hemoglobin greater than or equal to 8.0 mg/dL
• • ALT less than or equal to 287 (7 X the NIH upper limit of normal)
• • Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to dosing with study medications.
• • If capable of pregnancy: use of effective contraception during study: effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception
• • Willing and able to provide written informed consent
• • Because liver disease can result in encephalopathy, willing to designate a person for durable power of attorney on the NIH form for medical research and medical care purposes at the NIH Clinical Center
• EXCLUSION CRITERIA:
• • Prior use of ADV (outside of patient receiving adefovir from NIH under emergency use IND) or prior use of tenofovir, or cidofovir
• • Active serious systemic infections other than HIV or HBV
• • Liver disease caused by reasons other than hepatitis B e.g., HCV, HDV, Wilson's, hemochromatosis, autoimmune hepatitis (ANA greater than or equal to 160) except history of drug-associated hepatitis with discontinuation of causative agent
• • History of significant encephalopathy
• • History of clinically significant pancreatitis
• • History of untreated varices
• • New AIDS-defining event other than esophageal candidiasis diagnosed within one month prior to baseline
• • Decompensated heart failure
• • Treatment with immunomodulator drugs (interferons, interleukins, corticosteroids in greater than physiologic doses) in the 4 weeks prior to baseline. G-CSF and epoietin use are permitted.
• • Anti-HBV therapy other than lamivudine (such as emtricitabine, lobucavir, entecavir, HBIG, clevudine, MCC-478) with the exception of interferon alpha, famciclovir or foscarnet that ended more than 12 weeks prior to screen.
• • Hepatic mass suggestive of hepatocellular carcinoma
• • Alpha-fetoprotein level greater than or equal to 200ng/mL
• • Evidence of gastrointestinal malabsorption or chronic nausea or vomiting
• • Current alcohol or substance abuse that potentially could interfere with patient compliance
• • Malignancy other than cutaneous Kaposi's sarcoma, skin cancer treated by resection or HPV-associated carcinoma in situ or Bowen's disease in the 5 years prior to enrollment
• • History of clinically significant renal dysfunction within the previous 12 months prior to baseline
• • Concomitant therapy with aminoglycosides, amphotericin B, cidofivir, cisplatinum, IV pentamidine, vancomycin, systemic chemotherapeutic agents, probenecid or other nephrotoxic agents
• • Proteinuria (greater than or equal to 3+)
• • ANA greater than or equal to 3 EU
• • Positive PCR test for hepatitis C
• • Antibodies to hepatitis D (delta hepatitis)
• • Pregnancy or breast-feeding
• • History of organ or bone marrow transplantation
• • Any systemic illness that will make it unlikely that the subject will be able to return to NIH for the required study visits.