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HIV and Hepatitis.com Coverage of
DIGESTIVE DISEASE WEEK (DDW 2008)
May 17 - 22, 2008, San Diego, California

Combination Therapy with Lamivudine (Epivir-HBV) plus Adefovir (Hepsera) for Chronic Hepatitis B Prevents Resistance to Both Drugs

By Liz Highleyman

Hepatitis B Virus

Various nucleoside/nucleotide analogs are used to treat chronic hepatitis B virus (HBV) infection, but their long-term effectiveness is limited by the emergence of drug-resistant virus.

Resistance to lamivudine (Epivir-HBV), a common and inexpensive first-line agent, leads to resistance rates of about 25% after 1 year, about 50% after 2 years, and about 75% after 4 years of monotherapy. Resistance to another approved drug, adefovir (Hepsera) occurs in approximately 3%, 10%, and 30%, respectively.

As reported at the Digestive Disease Week 2008 conference last month in San Diego, Christophe Hezode and colleagues conducted a study to test the theory that combination therapy might reduce the development of viral resistance by raising the genetic barrier -- as has been amply demonstrated, for example, with combination antiretroviral therapy for HIV.

The investigators assessed the incidence and type of HBV resistance in patients treated with both lamivudine and adefovir. The study included 50 chronic hepatitis B patients in France. Most (74%) were men, the average age was 51 years, 68% were hepatitis B "e" antigen (HBeAg) negative, and 40% had liver cirrhosis.

Participants were treated with a combination of 100 mg once-daily lamivudine plus 10 mg once-daily adefovir for a median of 3 years. Patients were divided into 3 groups according to the timing of combination therapy initiation:

• Group 1 included 16 treatment-naive patients who started with combination therapy and were followed for a median 29 months.
• Group 2 included 9 patients currently receiving lamivudine monotherapy who added adefovir in the absence of any virological breakthrough and were followed for a median of 28 months.
• Group 3 consisted of 25 patients currently receiving lamivudine monotherapy who added adefovir after virological breakthrough and were followed for a median of 45 months.

Results

• Overall, only 2 patients (4%) experienced virological breakthrough while on combination therapy.
•

Among participants in Group 1 (de novo combination therapy):

• 13 (81.3%) had undetectable HBV DNA (< 12 IU/mL).
• None of the remaining 3 patients experienced virological breakthrough.
• No amino acid substitutions associated with HBV resistance to lamivudine or adefovir were detected.
•

Among participants in Group 2 (adding lamivudine without virological breakthrough):

• There were 2 cases of virological relapse.
• HBV genetic sequence analysis was impossible in 1 case due to low HBV DNA.
• In the other patient, combination therapy selected HBV variants with rtM204V + rtL180M + rtA181V substitutions, subsequently replaced by variants with only rtL180M + rtA181V.
•

" Among participants in Group 3 (adding lamivudine after virological breakthrough):

• 17 (68%) had undetectable HBV DNA at the end of follow-up.
• No virological breakthrough was observed in the remaining 8 patients.

Based on these findings, the investigators concluded that, "the combination of lamivudine and adefovir prevents the occurrence of both lamivudine and adefovir resistance in de novo and add-on strategies."

However, they added that the rtA181V substitution "confers resistance to both drugs and can (rarely) be responsible for HBV resistance under combination therapy."

6/10/08

Reference
C Hezode, V Dhalluin-Venier, S Chevaliez, and others. The combination of lamivudine and adefovir prevents both lamivudine and adefovir resistance in patients with chronic hepatitis B. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract M1919.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


















 

 

 

 

 

 

 

 

 

 

 


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