Efficacy and safety of entecavir for chronic HBV in HIV/HBV coinfected patients receiving lamivudine as part of antiretroviral therapy.

Abstract

BACKGROUND:

Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining suppression of plasma HIV RNA less than 400 copies/ml.

METHODS:

Sixty-eight patients were randomized to entecavir 1 mg (n = 51) or placebo (n = 17) once daily for 24 weeks; 65 patients continued the study with entecavir for an additional 24 weeks. Lamivudine-containing HAART was continued throughout.

RESULTS:

At week 24, the mean HBV DNA in entecavir-treated patients was 5.52 log10 copies/ml versus 9.27 log10 copies/ml for placebo, and at week 48, it was 4.79 log10 copies/ml versus 5.63 log10 copies/ml, respectively. The mean HBV DNA change from baseline for entecavir was -3.65 log10 copies/ml (versus + 0.11 for placebo, P < 0.0001) and alanine aminotransferase normalization in 34% of patients (versus 8% for placebo, P = 0.08). At 48 weeks, mean change in HBV DNA reached -4.20 log10 copies/ml in patients who received entecavir for the entire 48 weeks. The frequency of adverse events with entecavir and placebo was comparable. Through 48 weeks, no clinically relevant changes in HIV viremia or CD4 cell counts were identified.

CONCLUSION:

In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment.

• Authors: Mário Guimarães Pessôa, Brian Gazzard, Anna K Huang, Carlos E Brandão-Mello, Isabel Cassetti, Maria Cassia Mendes-Corrêa, Vicente Soriano, Phillip Phiri, Andrea Hall, Helena Brett-Smith
• Journal: AIDS (London, England) (AIDS) Vol. 22 Issue 14 Pg. 1779-87 (Sep 12 2008) ISSN: 1473-5571 [Electronic] England
• PMID: 18753861 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• DNA, Viral
• Lamivudine
• entecavir
• Guanine

Topics

• Adult
• Antiretroviral Therapy, Highly Active
• Antiviral Agents (therapeutic use)
• DNA, Viral (analysis)
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Guanine (adverse effects, analogs & derivatives, therapeutic use)
• HIV (genetics)
• HIV Infections (drug therapy, virology)
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (drug therapy, virology)
• Humans
• Lamivudine (therapeutic use)
• Linear Models
• Male
• Middle Aged
• Single-Blind Method
• Virus Replication (drug effects)