Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.
BACKGROUND
Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients.


METHODS
35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy.


RESULTS
Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count.


CONCLUSIONS
These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.
Benhamou
Y
Y
Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. ybenhamou@teaser.fr
Bochet
M
M
Thibault
V
V
Calvez
V
V
Fievet
M H
MH
Vig
P
P
Gibbs
C S
CS
Brosgart
C
C
Fry
J
J
Namini
H
H
Katlama
C
C
Poynard
T
T
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D063065:Organophosphonates; D010865:Pilot Projects; D019562:Viral Load
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil