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Adefovir Dipivoxil for the Treatment of Hepatitis B in Human Immunodeficiency Virus Infected Patients With Decompensated Hepatitis B Liver Disease and a Hepatitis B Viral Load of at Least 1.0 X 10(6) (Copies/mL) Despite 52 Weeks of Lamivudine Therapy

Phase 2
Not Enrolling
Hepatitis B, HIV Infection

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Trial Information

Adefovir Dipivoxil for the Treatment of Hepatitis B in Human Immunodeficiency Virus Infected Patients With Decompensated Hepatitis B Liver Disease and a Hepatitis B Viral Load of at Least 1.0 X 10(6) (Copies/mL) Despite 52 Weeks of Lamivudine Therapy

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 of viral load response to adefovir will be
assessed. Specimens will be stored for possible use in evaluating HBV and HIV resistance to
adefovir. L-carnitine supplementation will be used only if low serum carnitine levels are
documented. Patients will be followed for HBV viral load response to adefovir for 48 weeks
with possible extension. The primary study endpoints will be HBV viral load at week 24
(per-protocol patients) and DAVG at week 24 (intent-to-treat patients). Adefovir will be
discontinued for toxicity; there will be no dose reduction. Up to 30 subjects will be

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

Decompensated cirrhosis (Child-Pugh Score greater than or equal to 7: Class B or C

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


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

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

Concomitant therapy with aminoglycosides, amphotericin B, cidofivir, cisplatinum, IV
pentamidine, vancomycin, systemic chemotherapeutic agents, probenecid or other nephrotoxic

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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

March 2001

Completion Date:

February 2004

Related Keywords:

  • Hepatitis B
  • HIV Infection
  • Immunology
  • Cirrhosis
  • Ascites
  • Open-Label
  • Chronic
  • HIV
  • Hepatitis B
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Hepatitis
  • Hepatitis A
  • Hepatitis B



National Institute of Allergy and Infectious Diseases (NIAID) Bethesda, Maryland  20892