Adefovir dipivoxil promising for lamivudine-resistant HBV in HIV-1 infected patients

Preliminary data indicate that adefovir dipivoxil, an experimental nucleoside analogue, has significant antiviral activity against lamivudine-resistant hepatitis B virus (HBV) in patients co-infected with HIV-1.

Dr. Yves Benhamou and colleagues from Groupe Hospitalier Pitié-Salpétrière in Paris, in collaboration with researchers at Gilead Sciences, the developer of the drug, report the finding from an open-label pilot study in the September 1st issue of The Lancet.

In this trial, 35 HIV-1/HBV co-infected patients receiving 150 mg lamivudine twice daily as part of their antiretroviral regimen added 10 mg adefovir dipivoxil once daily for 48 weeks. Four patients withdrew from the study, two due to adverse events.

“Treatment with adefovir dipivoxil was associated with a significant and sustained reduction of HBV DNA in patients who had developed resistance to treatment with lamivudine, ” Dr. Benhamou said in comments to Reuters Health. Serum HBV DNA concentrations decreased an average of > log 4 copies/mL after 48 weeks of therapy, the team reports in the paper.

“This result has very positive clinical implications, particularly for patients who are co-infected with chronic HBV and HIV, because this group has very limited treatment options and can be susceptible to rapid progression of liver disease, ” he said.

Adefovir dipivoxil was “generally well tolerated, ” according to Dr. Benhamou, without any significant changes in serum electrolytes and renal function. Fifteen patients showed transient increases in serum alanine aminotransferase concentrations. The drug had no significant effect on HIV-1 RNA or CD4 cell count.

“We now know that within 4 years of treatment, up to 90% of patients co-infected with HBV and HIV-1 develop resistance to lamivudine, the only oral antiviral currently available for treatment of chronic HBV, ” Dr. Benhamou said. “As a physician, I am very encouraged to see the significant anti-HBV activity of adefovir dipivoxil, along with its tolerability, in this patient population.”

Dr. Benhamou said he is especially encouraged to see that after 48 weeks of treatment they have not observed the development of resistance mutations to adefovir dipivoxil.

“These findings have been confirmed in larger controlled Phase III clinical trials of the drug, leading me to believe that adefovir dipivoxil will be an important new drug for the treatment of chronic HBV infection, ” Dr. Benhamou added.

Gilead Sciences anticipates filing for US and European regulatory approval for adefovir dipivoxil use for HBV in the first 6 months of 2002.

Comment

Gilead have a protocol to provide ADV now on an individual patient basis for people who have critical need for this drug and clinicians are urged to contact Gilead if they have patients in this situation.

A full expanded access programme for ADV started in France in July. A programme for the UK is expected to start later this year or in early 2002, and is dependent to some extent on physician and community demand.

Clinicians should contact Dr Geoff Cotton at Gilead on 01223 579404 for information both for immediate access for this named patient access and the proposed expanded access programme.

Benhamou Y et al. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet 2001;358:718-723.
http://www.ncbi.nlm.nih.gov/pubmed/11551579?dopt=Abstract