Hepatitis B virus e antigen loss during adefovir dipivoxil therapy is associated with enhanced virus-specific CD4+ T-cell reactivity.

Abstract

Weak T-cell reactivity to hepatitis B virus (HBV) is thought to be the dominant cause for chronic HBV infection. Treatment with adefovir dipivoxil (ADV) increases the rate of HBV e antigen (HBeAg) loss; however, the immune mechanisms associated with this treatment response are not understood. Serial analysis of HBV-specific CD4+ T-cell reactivity was performed during 48 weeks of therapy with ADV and correlated with treatment outcome for 19 HBeAg-positive patients receiving ADV (n = 13) or the placebo (n = 6). We tested T-cell reactivity to HBV at seven protocol time points by proliferation, cytokine production, and enzyme-linked immunospot assays. A panel of serum cytokines was quantitated by cytokine bead array. ADV-treated patients showed increased CD4+ T-cell responses to HBV and lower serum levels of cytokines compared to those of placebo-treated patients. Enhanced CD4+ T-cell reactivity to HBV, which peaked at treatment week 16, was confined to a subgroup of ADV-treated patients who achieved greater viral suppression (5.3 +/- 0.3 log(10) copies/ml [mean +/- standard error of the mean {SEM}] serum HBV DNA reduction from baseline) and HBeAg loss, but not to ADV-treated patients with moderate (3.4 +/- 0.2 log(10) copies/ml [mean +/- SEM]) viremia reduction who remained HBeAg positive or to patients receiving the placebo. In conclusion, T-cell reactivity to HBV increases in a proportion of ADV-treated patients and is associated with greater suppression of HBV replication and HBeAg loss.

• Authors: Helen Cooksley, Shilpa Chokshi, Yafit Maayan, Heiner Wedemeyer, Pietro Andreone, Richard Gilson, Thomas Warnes, Simona Paganin, Fabien Zoulim, David Frederick, Avidan U Neumann, Carol L Brosgart, Nikolai V Naoumov
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 52 Issue 1 Pg. 312-20 (Jan 2008) ISSN: 0066-4804 [Print] United States
• PMID: 17984230 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Organophosphonates
• Reverse Transcriptase Inhibitors
• Adenine
• adefovir dipivoxil

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adult
• Antiviral Agents (therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• DNA, Viral (blood)
• Female
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, immunology)
• Hepatitis B, Chronic (drug therapy, virology)
• Humans
• Lymphocyte Activation (immunology)
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Reverse Transcriptase Inhibitors (therapeutic use)
• Treatment Outcome
• Virus Replication